De novo design of an artificial bis[4Fe-4S] binding protein.
In nature, protein subunits containing multiple iron-sulfur clusters often mediate the delivery of reducing equivalents from metabolic pathways to the active site of redox proteins. The de novo design of redox active proteins should include the engineering of a conduit for the delivery of electrons to and from the active site, in which multiple redox active centers are arranged in a controlled manner. Here, we describe a designed three-helix protein, DSD-bis[4Fe-4S], that coordinates two iron-sulfur clusters within its hydrophobic core. The design exploits the pseudo two-fold symmetry of the protein scaffold, DSD, which is a homodimeric three-helix bundle. Starting from the sequence of the parent peptide, we mutated eight leucine residues per dimer in the hydrophobic core to cysteine to provide the first coordination sphere for cubane-type iron-sulfur clusters. Incorporation of two clusters per dimer is readily achieved by in situ reconstitution and imparts increased stability to thermal denaturation compared to that of the apo form of the peptide as assessed by circular dichroism-monitored thermal denaturation. The presence of [4Fe-4S] clusters in intact proteins is confirmed by UV-vis spectroscopy, gel filtration, analytical ultracentrifugation, and electron paramagnetic resonance spectroscopy. Pulsed electron-electron double-resonance experiments have detected a magnetic dipole interaction between the two clusters ~0.7 MHz, which is consistent with the expected intercluster distance of 29-34 Å. Taken together, our data demonstrate the successful design of an artificial multi-iron-sulfur cluster protein with evidence of cluster-cluster interaction. The design principles implemented here can be extended to the design of multicluster molecular wires.


Increased CCN2 transcription in keloid fibroblasts requires cooperativity between AP-1 and SMAD binding sites.
We examined the transcriptional response to serum stimulation as an in vitro model of wound healing in keloid fibroblasts to identify molecular mechanisms leading to their aberrant growth. Keloids are proliferative dermal growths representing a pathologic wound healing response. Although several groups have shown increased expression of profibrotic factors in keloids, there is little known about why they are expressed at higher levels than normal. Fibroblasts derived from keloids and normal scar were subjected to serum stimulation as an in vitro model to mimic a component of the wound microenvironment to examine differential gene expression in keloid derived fibroblasts versus normal human fibroblasts. A promoter analysis was performed to identify specific enhancers involved in mediating the differential response of connective tissue growth factor (CTGF, CCN2). Point mutations in the enhancers were performed to confirm their role. Finally, we examined activation of transcription factors known to bind the targeted enhancers. Transcription of CCN2 after serum stimulation was significantly higher in keloid versus normal fibroblasts. Promoter analysis demonstrates the fragment from -625/-140 conferred increased serum responsiveness. Mutational analysis showed an AP-1 and SMAD binding site were both necessary for serum responsiveness. Preventing activation of either transcriptional complex will block CCN2 transcription. Additional experiments suggest that a single complex that includes components of the AP-1 and SMAD binding complexes is responsible for transactivation in response to serum. The key difference between keloid and normal fibroblasts appears to be the degree of activation of c-Jun. We suggest that altered responsiveness to cellular stress, based upon current data using serum stimulation and past data on response to mechanical strain, is a key defect leading to keloid formation.


The Stockholm breast cancer screening trial--5-year results and stage at discovery.
In screening programmes it is important to assess a preliminary effectiveness of the screening method as soon as possible in order to forecast survival figures. In March 1981 a controlled single-view mammographic screening trial for breast cancer was started in the south of Stockholm. The population invited for screening mammography consisted of 40,000 women aged 40-64 years, and 20,000 women served as a well-defined control group. The main aim of the trial was to determine whether repeated mammographic screening could reduce the mortality in the study population (SP) compared to the control population (CP). The cumulative number of advanced mammary carcinomas in the screening and the control populations from the first five years of screening have shown a tendency towards more favourable stages in the screened population aged 40-64 years. A breakdown by age suggests an effect in age group 50-59 years, but not yet in age groups 40-49 and 60-64 years. When comparing the rates of stage II+ cancer, an increased number is found in the study group. As the total rate of breast cancer is higher in SP than in CP, there ought to be a concealed group of stage II+ cancers in the CP which makes the comparison biased. A new approach has been designed, where an estimation of the 'hidden' number of stage II+ cancers in CP is added to the clinically detected cases, and in this respect a comparison has shown a decrease in the cumulative number of advanced cancers in the SP in relation to the CP (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Post-operative pulmonary complications in patients undergoing transoral odontoidectomy and posterior fixation for craniovertebral junction anomalies.
In patients with craniovertebral junction (CVJ) anomalies, the respiratory system is adversely affected in many ways. The sub-clinical manifestations may get aggravated in the postoperative period owing to anesthetic or surgical reasons. However, there is limited data on the incidence of postoperative pulmonary complications (PPCs) and associated risk factors in such patients, who undergo transoral odontoidectomy (TOO) and posterior fixation (PF) in the same sitting. Five years data of 178 patients with CVJ anomaly who underwent TOO and PF in the same sitting were analyzed retrospectively. Preoperative status, intraoperative variables, and PPCs were recorded. Patients were divided into two groups depending on the presence or absence of PPCs. Bivariate analysis was done to find out association between various risk factors and PPCs. Multivariate analysis was done to detect relative contribution of the factors shown to be significant in bivariate analysis. P < 0.05 was considered as significant. The incidence of PPCs was found to be 15.7%. Factors significantly associated with PPCs were American Society of Anesthesiologists grade higher than II, preoperative lower cranial nerves palsy and respiratory involvement, duration of surgery, and intraoperative blood transfusion. In multivariate analysis, blood transfusion was found to be the sole contributing factor. The patients who developed PPCs had significantly prolonged stay in ICU and hospital. Patients with CVJ anomaly are at increased risk of developing PPCs. There is a strong association between intraoperative blood transfusion and PPCs. Patients with PPCs stay in the ICU and hospital for a longer period of time.


Eradication of bovine brucellosis in the Azores, Portugal-Outcome of a 5-year programme (2002-2007) based on test-and-slaughter and RB51 vaccination.
Bovine brucellosis is an important contagious disease that can cause abortions and infertility in cattle, and can be transmitted to humans. Despite having an eradication programme in place since 1994, in 2000 the situation of bovine brucellosis due to Brucella abortus was not significantly improving in 3 of the 9 islands (Terceira, S. Miguel and S. Jorge) of the archipelago of Azores, an autonomous region of Portugal. Farming on these islands, particularly dairy, is extensive. Therefore, the use of RB51 vaccine, which does not induce antibodies detectable with routine brucellosis diagnostic tests, was implemented. This article reports the results of an eradication programme based on RB51 mass vaccination combined with test-and-slaughter, which was implemented in the Azores during the 2002-2007 period. During the first round of vaccination, both adult cows and heifers were vaccinated. Subsequently, only replacement stock aged 4-12 months, were immunized with RB51.The test-and-slaughter policy based on bulk milk ring test (MRT) and serological surveillance was maintained. During this period, the average brucellosis herd incidence, herd prevalence and individual prevalence decreased 69.26%, 39.26% and 75.41% respectively for the three above-mentioned islands. However, disease reduction approaching eradication was obtained only on the island of Terceira, where a high level of vaccine coverage was rapidly reached and regularly maintained together with strict application of a test-and-slaughter programme. This work shows that the RB51 vaccine could be a useful tool for eradicating bovine brucellosis in well-controlled epidemiological units provided that there is mass vaccine coverage for a sufficiently long period of time and it is combined with an appropriate test-and-slaughter programme.


Have News Reports on Suicide and Attempted Suicide During the COVID-19 Pandemic Adhered to Guidance on Safer Reporting?
Background: Associations between sensational news coverage of suicide and increases in suicidal behavior have been well documented. Amid growing concern over the impact of the COVID-19 pandemic on suicide rates, it is especially important that news coverage adheres to recommended standards. Method: We analyzed the quality and content of print and online UK news reports of possible COVID-19-related suicides and suicide attempts in the first 4 months of the pandemic (N = 285). Results: The majority of reports made explicit links between suicidal behavior and the COVID-19 pandemic in the headline (65.5%), largely based on statements by family, friends, or acquaintances of the deceased (60%). The impact of the pandemic on suicidal behavior was most often attributed to feelings of isolation (27.4%), poor mental health (14.7%), and entrapment due to government-imposed restrictions (14.4%). Although rarely of poor overall quality, reporting was biased toward young people, frontline staff, and relatively unusual suicides and, to varying degrees, failed to meet recommended standards (e.g., 41.1% did not signpost readers to sources of support). Limitations: This analysis cannot account for the impact of reporting on suicide. Conclusion: Careful attention must be paid to the quality and content of reports, especially as longer-term consequences of the pandemic develop.


Automatic facial mimicry in response to dynamic emotional stimuli in five-month-old infants.
Human adults automatically mimic others' emotional expressions, which is believed to contribute to sharing emotions with others. Although this behaviour appears fundamental to social reciprocity, little is known about its developmental process. Therefore, we examined whether infants show automatic facial mimicry in response to others' emotional expressions. Facial electromyographic activity over the corrugator supercilii (brow) and zygomaticus major (cheek) of four- to five-month-old infants was measured while they viewed dynamic clips presenting audiovisual, visual and auditory emotions. The audiovisual bimodal emotion stimuli were a display of a laughing/crying facial expression with an emotionally congruent vocalization, whereas the visual/auditory unimodal emotion stimuli displayed those emotional faces/vocalizations paired with a neutral vocalization/face, respectively. Increased activation of the corrugator supercilii muscle in response to audiovisual cries and the zygomaticus major in response to audiovisual laughter were observed between 500 and 1000 ms after stimulus onset, which clearly suggests rapid facial mimicry. By contrast, both visual and auditory unimodal emotion stimuli did not activate the infants' corresponding muscles. These results revealed that automatic facial mimicry is present as early as five months of age, when multimodal emotional information is present.


Glucocorticoid effects on memory function over the human life span.
Glucocorticoids (GCs), produced by the stress-responsive hypothalamic-pituitary-adrenal axis, are well recognized for their regulatory role in peripheral metabolism. GCs are also known to regulate various brain functions, with well-described effects on human cognition. Increased GC exposure in humans-including exposure to the endogenous GC, cortisol-at levels associated with stress, decreases memory and learning function. These results extend evidence from in vitro studies of synaptic and cell function and evidence from animals indicating the GCs can regulate substrates of memory function. While considerable evidence details these effects in adult humans and animals, relatively less is know about the effect of GCs on cognitive function in children and older adults. Investigators have suggested that children, particularly preschool-aged children, may be vulnerable to adverse consequences of increased GC secretion resulting from stress and neuropsychiatric diseases such as depression. Adverse GC effects on memory substrates and memory function in the adult have also fostered concern that age-related changes, including changes in GC receptors and changes in circulating cortisol levels, could lead to age-related increases in the adverse effect of GCs on brain function. Investigators have reported an association between age-related increases in cortisol levels and age-related memory decline, but this association may or may not be due to a direct effect of cortisol on memory substrates. A number of possible treatment approaches to prevent or remediate adverse GC-induced effects are under development. In general, the use of safe and effective agents for blocking adverse GC effects on brain functions including memory may offer benefits to individuals suffering acute and chronic stressors and could prevent brain changes relevant to stress, aging, and stress-related neuropsychiatric diseases.


[Therapeutic approach targeting TRP channels and development of anti-aspiration drugs].
Aspiration pneumonia is a major health problem in the elderly. A swallowing disorder, such as a delayed triggering of the swallowing reflex, predisposes in patients with aspiration pneumonia. Swallowing reflex was delayed when the temperature of the food is close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive TRP channel at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, we found anti-aspiration drugs with various site of actions on the hierarchical structure of neuronal control of swallowing. By combining anti-aspiration drugs and swallowing rehabilitations, we developed a protocol to start eating more efficiently and safely. Implementation of this protocol would help avoid re-aspiration in many elderly people with aspiration pneumonia. The combination of various anti-aspiration drugs may improve the swallowing disorders and prevent aspiration pneumonia.


Keratomalacia in a child with familial hypo-retinol-binding proteinemia.
Retinol-binding protein (RBP) is a plasma protein with a molecular weight of 21,000 synthesized in the hepatocytes, binding with retinol (vitamin A), and transporting retinol to peripheral tissues. Keratomalacia is caused by a deficiency of vitamin A itself and/or protein-calorie malnutrition. In the latter condition, production of RBP is inhibited. We report herein familial hypo-retinol-binding proteinemia in a child aged 19 months who developed keratomalacia during measles infection in spite of good nourishment. To the best of our knowledge this is the first description of such a case. The patient, her sister and mother showed persistent low levels, about half the normal levels, of retinol and RBP which were unresponsive to oral vitamin A and protein-rich diet. They had normal liver function tests, normal serum levels of other proteins and fat-soluble vitamins and lipids. This hypo-retinol-binding proteinemia was thought to predispose the child to develop keratomalacia during measles. Family members would be heterozygous with one normal RBP gene and one defective RBP gene.


EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis.
Atopic dermatitis (AD) is a common, complex, and highly heritable inflammatory skin disease. Genome-wide association studies offer opportunities to identify molecular targets for drug development. A risk locus on chromosome 11q13.5 lies between 2 candidate genes, EMSY and LRRC32 (leucine-rich repeat-containing 32) but the functional mechanisms affecting risk of AD remain unclear. We sought to apply a combination of genomic and molecular analytic techniques to investigate which genes are responsible for genetic risk at this locus and to define mechanisms contributing to atopic skin disease. We used interrogation of available genomic and chromosome conformation data in keratinocytes, small interfering RNA (siRNA)-mediated knockdown in skin organotypic culture and functional assessment of barrier parameters, mass spectrometric global proteomic analysis and quantitative lipid analysis, electron microscopy of organotypic skin, and immunohistochemistry of human skin samples. Genomic data indicate active promoters in the genome-wide association study locus and upstream of EMSY; EMSY, LRRC32, and intergenic variants all appear to be within a single topologically associating domain. siRNA-knockdown of EMSY in organotypic culture leads to enhanced development of barrier function, reflecting increased expression of structural and functional proteins, including filaggrin and filaggrin-2, as well as long-chain ceramides. Conversely, overexpression of EMSY in keratinocytes leads to a reduction in markers of barrier formation. Skin biopsy samples from patients with AD show greater EMSY staining in the nucleus, which is consistent with an increased functional effect of this transcriptional control protein. Our findings demonstrate an important role for EMSY in transcriptional regulation and skin barrier formation, supporting EMSY inhibition as a therapeutic approach.


Biological control of take-all by fluorescent Pseudomonas spp. from Chinese wheat fields.
Take-all disease of wheat caused by the soilborne fungus Gaeumannomyces graminis var. tritici is one of the most important root diseases of wheat worldwide. Bacteria were isolated from winter wheat from irrigated and rainfed fields in Hebei and Jiangsu provinces in China, respectively. Samples from rhizosphere soil, roots, stems, and leaves were plated onto King's medium B agar and 553 isolates were selected. On the basis of in vitro tests, 105 isolates (19% of the total) inhibited G. graminis var. tritici and all were identified as Pseudomonas spp. by amplified ribosomal DNA restriction analysis. Based on biocontrol assays, 13 strains were selected for further analysis. All of them aggressively colonized the rhizosphere of wheat and suppressed take-all. Of the 13 strains, 3 (HC9-07, HC13-07, and JC14-07, all stem endophytes) had genes for the biosynthesis of phenazine-1-carboxylic acid (PCA) but none had genes for the production of 2,4-diacetylphloroglucinol, pyoluteorin, or pyrrolnitrin. High-pressure liquid chromatography (HPLC) analysis of 2-day-old cultures confirmed that HC9-07, HC13-07, and JC14-07 produced PCA but no other phenazines were detected. HPLC quantitative time-of-flight 2 mass-spectrometry analysis of extracts from roots of spring wheat colonized by HC9-07, HC13-07, or Pseudomonas fluorescens 2-79 demonstrated that all three strains produced PCA in the rhizosphere. Loss of PCA production by strain HC9-07 resulted in a loss of biocontrol activity. Analysis of DNA sequences within the key phenazine biosynthesis gene phzF and of 16S rDNA indicated that strains HC9-07, HC13-07, and JC14-07 were similar to the well-described PCA producer P. fluorescens 2-79. This is the first report of 2-79-like bacteria being isolated from Asia.


Primitive, and protective, our cellular oxygenation status?
The primitive atmosphere where aerobic life started on earth was hypoxic and hypercapnic. Remarkably, an adaptation strategy whereby O2 partial pressure, PO2, in the arterial blood is maintained within a low and narrow range of 1-3 kPa, largely independent of inspired PO2, has also been reported in modern water-breathers. In mammalian tissues, including brain, the most frequently measured PO2 is also in the same low range. Based on the postulate that basic cellular machinery has been established since the early stages of evolution, we propose that this similarity in oxygenation status is the consequence of an early adaptation strategy which, subsequently, throughout the course of evolution, maintained cellular oxygenation in the same low and primitive range independent of environmental changes. Specialized enzymes aimed at protecting cells against O2 toxicity are thought to have appeared very early in evolution but we suggest that preventing high PO2's is also the simplest and most efficient tool for limiting reactive oxygen species (ROS) production. It could be a cue mechanism to widen our understanding of the ageing process.


Helicoidal transfer matrix model for inhomogeneous DNA melting.
An inhomogeneous helicoidal nearest-neighbor model with continuous degrees of freedom is shown to predict the same DNA melting properties as traditional long-range Ising models, for free DNA molecules in solution, as well as superhelically stressed DNA with a fixed linking number constraint. Without loss of accuracy, the continuous degrees of freedom can be discretized using a minimal number of discretization points, yielding an effective transfer matrix model of modest dimension (d=36). The resulting algorithms to compute DNA melting profiles are both simple and efficient.


The influence of ceramic surface treatments on the tensile bond strength of composite resin to all-ceramic coping materials.
An increasing demand for esthetic restorations has resulted in the development of new ceramic systems, but the fracture of veneering ceramics still remains the primary cause of failure. Porcelain repair frequently involves replacement with composite resin, but the bond strength between composite resin and all-ceramic coping materials has not been studied extensively. The purpose of this study was to evaluate the tensile bond strength of composite resin to 3 different all-ceramic coping materials with various surface treatments. Thirty specimens (10 x 10 x 2 mm) each of lithium-disilicate ceramic (IPS Empress2 [E]), alumina ceramic (In-Ceram Alumina [I]), and zirconia ceramic (Zi-Ceram [Z]) were fabricated. Feldspathic ceramic (Duceram Plus [F]) was used as the control. Each material was divided into 3 groups (n=10), and 3 different surface treatments were performed: airborne-particle abrasion with 50-microm alumina particles (Ab); airborne-particle abrasion with 50-microm alumina particles and acid etching with 4% hydrofluoric acid (Ae); or airborne-particle abrasion with 30-microm alumina particles modified with silica acid (Si). After surface treatment of ceramic specimens, composite resin cylinders (5-mm diameter x 10-mm height) were light polymerized onto the ceramic specimens. Each specimen was subjected to a tensile load at a crosshead speed of 2 mm/min until fracture. The fracture sites were examined with scanning electron microscopy to determine the location of failure during debonding and to examine the surface treatment effects. Two-way analysis of variance and the Duncan multiple comparison test (alpha=.05) were used to analyze the bond strength values. There were significant differences in the bond strengths for both ceramics (P<.001) and surface treatments (P<.001) and the interaction (P<.001). The Duncan analysis yielded the following statistical subsets of the bond strength values: (FAe, ISi, EAe, ZSi) > FAb > (FSi, EAb, ESi) (IAb, IAe) > (ZAe, ZAb). The results illustrate no differences within the parentheses but statistically significant differences among the groups. Alumina and zirconia ceramic specimens treated with a silica coating technique, and lithium disilicate ceramic specimens treated with airborne-particle abrasion and acid etching yielded the highest tensile bond strength values to a composite resin for the materials tested.


Quantifying the effect of straylight on photopic contrast sensitivity.
The visual performance of a reference group (RG) using diffuser filters was compared to a cataract-diagnosed group (CatG). Measurements of straylight (SL) parameter, photopic contrast sensitivity (CS), and visual acuity (VA) were carried out in both groups. Before the analysis, the performance of the instruments used for this purpose was tested. The RG was comprised of three healthy, young eyes (25-30 years old) while 59 subjects (aged 50-80 years old) with lens opacities were recruited for the CatG. Six diffuser conditions were tested in the RG. To discriminate between light scattering levels, SL measurements proved to be most sensitive, VA did not discriminate at all, while CS showed intermediate sensitivity. VA was not correlated with SL, while the correlation between CS and SL was significant (p<0.05) in both groups. Since the correlation in the RG was particularly strong, parameters of a linear regression model are presented. The behavior of CS as a function of SL was comparable to some extent between RG and CatG.


Phase noise and phase modulation in optical coherence tomography.
The signal in optical coherence tomography is often modulated either in phase or by use of the Doppler modulation generated by a depth-scanning mechanism. The effect of each type of modulation on the signal's amplitude is evaluated. The advantages of each type of modulation in terms of immunity to phase noise and penetration depth are discussed in relation to two envelope detection schemes, i.e., lock-in detection and rms-to-dc conversion. Phase noise due to drifts and demodulation instabilities causes distortion of the signal envelope and can be responsible in part for the speckle appearance of the image.


Early-onset inflammatory responses in vivo to adenoviral vectors in the presence or absence of lipopolysaccharide-induced inflammation.
Adenoviral vectors (Ad) have potential for use in pulmonary gene transfer for treating cystic fibrosis (CF). However, Ad may induce inflammation even in the absence of gene expression. Endotoxin from gram-negative bacteria in the airways of CF patients may also induce inflammation, and may further inhibit vector delivery and gene transfer. We used a mouse model to study the time course of Ad-induced lung inflammation and to assess additivity with lipopolysaccharide (LPS)-induced inflammatory responses. C3H/HeJ endotoxin-resistant (RES) mice hyporesponsive to inflammatory stimuli and normoresponsive C3HeB/FeJ endotoxin-sensitive (SEN) mice were studied to characterize inflammatory responses that follow intratracheal instillation of inactivated Ad, with or without simultaneous inhalation exposure to LPS. Instillation of 10(10) Ad particles dramatically increased bronchoalveolar lavage fluid (BALF) concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 at 3 to 6 h and induced profound neutrophilia, maximal at 12 to 24 h. SEN mice had tenfold greater responses than did RES mice at 6, 12, and 24 h. Mice exposed to Ad alone, LPS alone, or Ad + LPS had significant inflammation at the 3-h time point as demonstrated by BALF neutrophils, TNF-alpha, and IL-6. With all three treatments, SEN mice had a five- to 300-fold greater response than did RES mice. Importantly, Ad + LPS yielded no greater inflammatory response than LPS without Ad. These data demonstrate that replication-deficient Ad induce early inflammation and LPS-induced inflammation is not augmented by concurrent treatment with Ad.


Encapsulation of Bioactive Compounds for Food and Agricultural Applications.
This review presents an updated scenario of findings and evolutions of encapsulation of bioactive compounds for food and agricultural applications. Many polymers have been reported as encapsulated agents, such as sodium alginate, gum Arabic, chitosan, cellulose and carboxymethylcellulose, pectin, Shellac, xanthan gum, zein, pullulan, maltodextrin, whey protein, galactomannan, modified starch, polycaprolactone, and sodium caseinate. The main encapsulation methods investigated in the study include both physical and chemical ones, such as freeze-drying, spray-drying, extrusion, coacervation, complexation, and supercritical anti-solvent drying. Consequently, in the food area, bioactive peptides, vitamins, essential oils, caffeine, plant extracts, fatty acids, flavonoids, carotenoids, and terpenes are the main compounds encapsulated. In the agricultural area, essential oils, lipids, phytotoxins, medicines, vaccines, hemoglobin, and microbial metabolites are the main compounds encapsulated. Most scientific investigations have one or more objectives, such as to improve the stability of formulated systems, increase the release time, retain and protect active properties, reduce lipid oxidation, maintain organoleptic properties, and present bioactivities even in extreme thermal, radiation, and pH conditions. Considering the increasing worldwide interest for biomolecules in modern and sustainable agriculture, encapsulation can be efficient for the formulation of biofungicides, biopesticides, bioherbicides, and biofertilizers. With this review, it is inferred that the current scenario indicates evolutions in the production methods by increasing the scales and the techno-economic feasibilities. The Technology Readiness Level (TRL) for most of the encapsulation methods is going beyond TRL 6, in which the knowledge gathered allows for having a functional prototype or a representative model of the encapsulation technologies presented in this review.


First record of Calliephialtes sittenfeldae associated with the tephritid fruit fly Anastrepha spatulata in Mexico.
This paper reports for the first time an ichneumonid parasitoid Calliephialtes sittenfeldae Gauld Ugalde-Gómez et Hanson (Hymenoptera: Ichneumonidae) associated with a dipteran host Anastrepha spatulata Stone (Diptera: Tephritidae), recovered from fruit of Schoepfia schreberi (Santalales: Olacaceae) in central Veracruz, Mexico. Large numbers of this parasitoid were collected and reared from its fruit fly host in three localities of Veracruz, Mexico. Some observations of its biology are also reported. This is a first record of C. sittenfeldae from Mexico, and the first record of this parasitoid species, its insect host, and the host plant. The male of this species is described and illustrated for the first time.


Evidence for persistent Chlamydia pneumoniae infection of human coronary atheromas.
To date, structures representing developmental stages of Chlamydia pneumoniae, especially persistent forms of this intracellular bacteria, have not been described in human atherosclerotic tissues using specific antibody labeling and transmission electron microscopy. Staining of atherosclerotic tissue from five patients seeking heart transplantation with gold-labeled antibodies specific for up-regulated chlamydial heat shock proteins, GroEL and GroES, and visualisation via transmission electron microscopy revealed intracellular, atypical, round to oval structures of variable diameter. These structures resembled reticulate bodies of Chlamydia, were surrounded by membranes and were located within smooth muscle cells, macrophages or fibroblasts. By using double immunogold electron microscopy technique (GroEL and GroES in combination with chlamydial LPS/MOMP antibodies), we demonstrated these structures were of chlamydial origin. In the current study, we demonstrated the presence of aberrant bodies of C. pneumoniae in vivo in archival coronary atheromatous heart tissues by the immunogold electron microscopy technique.


Identifying asymptomatic patients at high-risk for stroke.
Carotid endarterectomy and carotid artery stenting, in addition to good medical therapy, halve long-term stroke risk in asymptomatic patients with carotid artery stenosis. Since the absolute benefits following successful intervention are moderate, identification of asymptomatic patients at high-risk of future stroke could maximize the effectiveness of carotid interventions. The aim of this paper is to summarize the evidence for high-risk features associated with increased long-term stroke risk in asymptomatic patients. There is a paucity of reliable data describing the effect of clinical features, imaging findings and plaque characteristics on increased long-term stroke risk. Clinical and imaging features such as contralateral symptoms, silent brain infarcts/embolic signals, progression of stenosis and impaired cerebrovascular reactivity may be associated with increased future risk of stroke. Plaque characteristics such as echolucency, large plaque size (≥80 mm), intra-plaque hemorrhage, lipid-rich necrotic core and thinned/ruptured fibrous cap may also increase future risk of stroke. Whilst these form the basis for European guidelines targeting carotid intervention in asymptomatic patients with tight stenosis, conclusive evidence of their utility is lacking. Results from ongoing large, multicenter randomized clinical trials comparing carotid endarterectomy and carotid artery stenting with good medical therapy may be consistent with earlier trials, showing a halving of the long-term risk of stroke following successful carotid revascularization. However, they may well lack sufficient statistical power to identify higher-risk subgroups in whom the absolute gains of treatment are significantly higher. Large contemporary cohort studies are needed to provide further clarity regarding high-risk features associated with increased long-term stroke risk in asymptomatic patients with carotid artery stenosis.


Determining the cost of obesity and its common comorbidities from a commercial claims database.
What is already known about this subject Obesity is highly prevalent and costly in the US. Obesity often leads to other comorbid conditions, including diabetes and hypertension. Obesity prevention efforts can reduce healthcare costs. What this study adds Obesity combined with other comorbidities significantly increases healthcare costs per patient visit. The combination of obesity and depression exacerbates costs. The most expensive series of chronic conditions in this study included obesity, diabetes, hypertension and depression. Our objectives were to determine payments made by commercial healthcare providers in the US for adults diagnosed with obesity, and those comorbid with any combination of selected chronic conditions. Using a commercial claims and encounters database (n = 3,562,717), we evaluated an adult study population that had at least one in-patient visit, outpatient visit or emergency department visit, and received a primary or secondary diagnosis of obesity. Persons were categorized by one or more comorbid diagnoses for diabetes mellitus, hypertension, depression or congestive heart failure. We adjusted for age and gender, and calculated the mean total net expenditures (in 2012, $US) for each combination of comorbid conditions based on individual visits to an in-patient, outpatient or emergency department setting. Among 50,717 claims with diagnosis of obesity, the mean net expenditure for in-patient and outpatient services was $ 1907 per patient per visit. Persons diagnosed with obesity and other comorbidities observed an increase in total net expenditures. Obesity and congestive heart failure observed the highest increase among single comorbidities at $ 5275. For persons with obesity and two other comorbidities, diabetes mellitus and depression was the highest at $ 15,226. The most expensive condition was obesity, diabetes mellitus, hypertension and depression at $ 15,733. Compared with average medical claims, persons diagnosed with obesity and other common chronic conditions experience significant increases in medical costs. These costs are often driven higher by time spent as in-patients. By controlling and reducing the prevalence of obesity, we may see significant decreases in medical expenditures.


Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides.
Δ(9)-Tetrahydrocannabinol (THC) and other cannabinoids are responsible for the psychoactive and medicinal properties of Cannabis sativa L. (marijuana). The first intermediate in the cannabinoid biosynthetic pathway is proposed to be olivetolic acid (OA), an alkylresorcinolic acid that forms the polyketide nucleus of the cannabinoids. OA has been postulated to be synthesized by a type III polyketide synthase (PKS) enzyme, but so far type III PKSs from cannabis have been shown to produce catalytic byproducts instead of OA. We analyzed the transcriptome of glandular trichomes from female cannabis flowers, which are the primary site of cannabinoid biosynthesis, and searched for polyketide cyclase-like enzymes that could assist in OA cyclization. Here, we show that a type III PKS (tetraketide synthase) from cannabis trichomes requires the presence of a polyketide cyclase enzyme, olivetolic acid cyclase (OAC), which catalyzes a C2-C7 intramolecular aldol condensation with carboxylate retention to form OA. OAC is a dimeric α+β barrel (DABB) protein that is structurally similar to polyketide cyclases from Streptomyces species. OAC transcript is present at high levels in glandular trichomes, an expression profile that parallels other cannabinoid pathway enzymes. Our identification of OAC both clarifies the cannabinoid pathway and demonstrates unexpected evolutionary parallels between polyketide biosynthesis in plants and bacteria. In addition, the widespread occurrence of DABB proteins in plants suggests that polyketide cyclases may play an overlooked role in generating plant chemical diversity.


Inhibitory effects of cranberry polyphenol and volatile extracts on nitric oxide production in LPS activated RAW 264.7 macrophages.
Cranberry volatiles have received little attention for health-promoting properties. In this study, we compared the inhibitory effects of cranberry polyphenol and volatile extracts and volatile standards on nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophages. Polyphenols were analyzed by HPLC/HPLC-MS and volatiles were analyzed by GC/GC-MS. The inhibition of NO production of the fresh cranberry polyphenol and volatile extracts and α-terpineol, linalool, linalool oxide, and eucalyptol standards at 2, 4, and 8-fold dilutions of their original concentrations in fresh cranberries was evaluated by treating these extracts/standards for 1 h before or after LPS application for 24 h. After inducing inflammation with LPS, the polyphenol treatments (317.8 and 635.7 μg g-1) and 1.8 μg g-1 volatile treatment lowered NO levels 46-62% compared to the positive control (P < 0.05). When the cells were treated with polyphenol and volatile extracts before inducing inflammation, the 635.7 μg g-1 and 317.8 μg g-1 polyphenol treatments and 1.8 μg g-1 and 0.9 μg g-1 volatile treatments lowered NO levels (13-52%) compared to the positive control (P < 0.05). Polyphenol and volatile extracts from cranberry were effective in reducing NO production whether applied before or after the application of LPS. α-Terpineol at a concentration found in fresh cranberries (1.16 μg mL-1) was also found to be effective in reducing NO production whether cells were treated before or after application of LPS. Future studies are needed to reveal the mechanisms by which volatile compounds, especially α-terpineol act to mitigate inflammation and to determine the bioavailability of terpenes.


Intravenous administration issues: a comparison of intravenous insertions and complications in vancomycin versus other antibiotics.
Nurses on a surgical unit compared 2 groups of patients, vancomycin versus other antibiotics, to determine whether vancomycin intravenous therapy is associated with more peripheral intravenous (PIV) complications. Data were collected on a number of PIV attempts and insertions, phlebitis and infiltration scores, nursing time, and missing or late doses on 153 orthopedic and trauma patients. Increased adverse outcomes were found with repeat venipunctures, attempts, nursing time, and infiltration. Patients receiving vancomycin through a PIV catheter developed more complications than those receiving other antibiotics. This is increasingly important because nurses make recommendations for vascular catheters.


Tackling inequalities in obesity: a protocol for a systematic review of the effectiveness of public health interventions at reducing socioeconomic inequalities in obesity amongst children.
There is growing evidence of the impact of overweight and obesity on short- and long-term functioning, health and well-being. Internationally, childhood obesity rates continue to rise in some countries (for example, Mexico, India, China and Canada), although there is emerging evidence of a slowing of this increase or a plateauing in some age groups. In most European countries, the United States and Australia, however, socioeconomic inequalities in relation to obesity and risk factors for obesity are widening. Addressing inequalities in obesity, therefore, has a very high profile on the public health and health services agendas. However, there is a lack of accessible policy-ready evidence on what works in terms of interventions to reduce inequalities in obesity. This article describes the protocol for a National Health Service Trust (NHS) National Institute for Health Research-funded systematic review of public health interventions at the individual, community and societal levels which might reduce socioeconomic inequalities in relation to obesity amongst children ages 0 to 18 years. The studies will be selected only if (1) they included a primary outcome that is a proxy for body fatness and (2) examined differential effects with regard to socioeconomic status (education, income, occupation, social class, deprivation and poverty) or the intervention was targeted specifically at disadvantaged groups (for example, children of the unemployed, lone parents, low income and so on) or at people who live in deprived areas. A rigorous and inclusive international literature search will be conducted for randomised and nonrandomised controlled trials, prospective and retrospective cohort studies (with and/or without control groups) and prospective repeat cross-sectional studies (with and/or without control groups). The following electronic databases will be searched: MEDLINE, Embase, CINAHL, PsycINFO, Social Science Citation Index, ASSIA, IBSS, Sociological Abstracts and the NHS Economic Evaluation Database. Database searches will be supplemented with website and grey literature searches. No studies will be excluded on the basis of language, country of origin or publication date. Study inclusion, data extraction and quality appraisal will be conducted by two reviewers. Meta-analysis and narrative synthesis will be conducted. The main analysis will examine the effects of (1) individual, (2) community and (3) societal level public health interventions on socioeconomic inequalities in childhood obesity. Interventions will be characterised by their level of action and their approach to tackling inequalities. Contextual information on how such public health interventions are organised, implemented and delivered will also be examined. In this review, we consider public health strategies which reduce and prevent inequalities in the prevalence of childhood obesity, highlight any gaps in the evidence base and seek to establish how such public health interventions are organised, implemented and delivered. PROSPERO registration number: CRD42011001740.


5-Methyldeoxycytidine enhances the substrate activity of DNA polymerase.
Here, we first demonstrated that 5-MedCTP could be incorporated into the synthetic DNA template by the exonuclease deficient Klenow fragment with a much higher efficiency than dCTP and 5-hydroxymethyl-dCTP. Further, we first conducted a comparable study of primer extension reaction using templates containing deoxycytidine (dC) or 5-methyldeoxycytidine (5-mdC) for incorporating different triphosphates. Based on our findings, 5-methyldeoxycytidine could enhance the substrate activity of the Klenow fragment (exo-) and this feature could potentially be used in DNA methylation analysis.


Modeling lung cancer evolution and preclinical response by orthotopic mouse allografts.
Cancer evolution is a process that is still poorly understood because of the lack of versatile in vivo longitudinal studies. By generating murine non-small cell lung cancer (NSCLC) orthoallobanks and paired primary cell lines, we provide a detailed description of an in vivo, time-dependent cancer malignization process. We identify the acquisition of metastatic dissemination potential, the selection of co-driver mutations, and the appearance of naturally occurring intratumor heterogeneity, thus recapitulating the stochastic nature of human cancer development. This approach combines the robustness of genetically engineered cancer models with the flexibility of allograft methodology. We have applied this tool for the preclinical evaluation of therapeutic approaches. This system can be implemented to improve the design of future treatments for patients with NSCLC.


Decreased frontal gyrification correlates with altered connectivity in children with autism.
The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anisotropy (FA) and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism.


Comparative genomic analysis of Campylobacter jejuni associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity.
Campylobacter jejuni infection represents the most frequent antecedent infection triggering the onset of the neuropathic disorders Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Although sialylated ganglioside-mimicking lipo-oligosaccharide (LOS) structures are the strongest neuropathogenic determinants in C. jejuni, they do not appear to be the only requirement for a neuropathic outcome since strains capable of their production have been isolated from patients with uncomplicated cases of enteritis. Consequently, other pathogen and/or host-related factors contribute to the onset of neurological complications. We have used comparative genomic hybridization to perform a detailed genomic comparison of strains isolated from GBS/MFS and enteritis-only patients. Our dataset, in which the gene conservation profile for 1712 genes was assayed in 102 strains, including 56 neuropathogenic isolates, represents the largest systematic search for C. jejuni factors associated with GBS/MFS to date and has allowed us to analyze the genetic background of neuropathogenic C. jejuni strains with an unprecedented level of resolution. The majority of GBS/MFS strains can be assigned to one of six major lineages, suggesting that several genetic backgrounds can result in a neuropathogenic phenotype. A statistical analysis of gene conservation rates revealed that although genes involved in the sialylation of LOS structures were significantly associated with neuropathogenic strains, still many enteritis-control strains both bear these genes and share remarkable levels of genomic similarity with their neuropathogenic counterparts. Two capsule biosynthesis genes (Cj1421c and Cj1428c) showed higher conservation rates among neuropathogenic strains compared to enteritis-control strains. Any potential involvement of these genes in neuropathogenesis must be assessed. A single gene (HS:3 Cj1135) had a higher conservation rate among enteritis-control strains. This gene encodes a glucosyltransferase that is found in some of the LOS classes that do not express ganglioside mimics. Our findings corroborate that neuropathogenic factors may be transferred between unrelated strains of different genetic background. Our results would also suggest that the failure of some strains isolated from uncomplicated cases of enteritis to elicit a neuropathic clinical outcome may be due to subtle genetic differences that silence their neuropathogenic potential and/or due to host-related factors.


An ethical and prudential argument for prioritizing the reduction of parasite-stress in the allocation of health care resources.
The link between parasite-stress and complex psychological dispositions implies that the social, political, and economic benefits likely to flow from public health interventions that reduce rates of non-zoonotic infectious disease are far greater than have traditionally been thought. We sketch a prudential and ethical argument for increasing public health resources globally and redistributing these to focus on the alleviation of parasite-stress in human populations.


Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles.
To develop clinical, demographic, and pathological profiles of young competitive athletes who died suddenly. Systematic evaluation of clinical information and circumstances associated with sudden deaths; interviews with family members, witnesses, and coaches; and analyses of postmortem anatomic, microscopic, and toxicologic data. A total of 158 sudden deaths that occurred in trained athletes throughout the United States from 1985 through 1995 were analyzed. MAIN OUTCOME MEASURES--Characteristics and probable cause of death. Of 158 sudden deaths among athletes, 24 (15%) were explained by noncardiovascular causes. Among the 134 athletes who had cardiovascular causes of sudden death, the median age was 17 years (range, 12-40 years), 120 (90%) were male, 70 (52%) were white, and 59 (44%) were black. The most common competitive sports involved were basketball (47 cases) and football (45 cases), together accounting for 68% of sudden deaths. A total of 121 athletes (90%) collapsed during or immediately after a training session (78 cases) or a formal athletic contest (43 cases), with 80 deaths (63%) occurring between 3 PM and 9 PM. The most common structural cardiovascular diseases identified at autopsy as the primary cause of death were hypertrophic cardiomyopathy (48 athletes [36%]), which was disproportionately prevalent in black athletes compared with white athletes (48% vs 26% of deaths; P = .01), and malformations involving anomalous coronary artery origin (17 athletes [13%]). Of 115 athletes who had a standard preparticipation medical evaluation, only 4 (3%) were suspected of having cardiovascular disease, and the cardiovascular abnormality responsible for sudden death was correctly identified in only 1 athlete (0.9%). Sudden death in young competitive athletes usually is precipitated by physical activity and may be due to a heterogeneous spectrum of cardiovascular disease, most commonly hypertrophic cardiomyopathy. Preparticipation screening appeared to be of limited value in identification of underlying cardiovascular abnormalities.


Maternal mortality in six low and lower-middle income countries from 2010 to 2018: risk factors and trends.
Maternal mortality is a public health problem that disproportionately affects low and lower-middle income countries (LMICs). Appropriate data sources are lacking to effectively track maternal mortality and monitor changes in this health indicator over time. We analyzed data from women enrolled in the NICHD Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR) from 2010 through 2018. Women delivering within research sites in the Democratic Republic of Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia are included. We evaluated maternal and delivery characteristics using log-binomial models and multivariable models to obtain relative risk estimates for mortality. We used running averages to track maternal mortality ratio (MMR, maternal deaths per 100,000 live births) over time. We evaluated 571,321 pregnancies and 842 maternal deaths. We observed an MMR of 157 / 100,000 live births (95% CI 147, 167) across all sites, with a range of MMRs from 97 (76, 118) in the Guatemala site to 327 (293, 361) in the Pakistan site. When adjusted for maternal risk factors, risks of maternal mortality were higher with maternal age > 35 (RR 1.43 (1.06, 1.92)), no maternal education (RR 3.40 (2.08, 5.55)), lower education (RR 2.46 (1.54, 3.94)), nulliparity (RR 1.24 (1.01, 1.52)) and parity > 2 (RR 1.48 (1.15, 1.89)). Increased risk of maternal mortality was also associated with occurrence of obstructed labor (RR 1.58 (1.14, 2.19)), severe antepartum hemorrhage (RR 2.59 (1.83, 3.66)) and hypertensive disorders (RR 6.87 (5.05, 9.34)). Before and after adjusting for other characteristics, physician attendance at delivery, delivery in hospital and Caesarean delivery were associated with increased risk. We observed variable changes over time in the MMR within sites. The MNHR is a useful tool for tracking MMRs in these LMICs. We identified maternal and delivery characteristics associated with increased risk of death, some might be confounded by indication. Despite declines in MMR in some sites, all sites had an MMR higher than the Sustainable Development Goals target of below 70 per 100,000 live births by 2030. The MNHR is registered at NCT01073475 .


Advances in gynaecological oncology surgery.
Latest surgical advances in the field of gynaecological oncology, a sub-specialty of gynaecology, are reviewed in this chapter. The surgery is mainly practised in cancer centres by board-certified gynaecologists, and requires a 2-3 year period of additional training in gynaecological oncology. Surgical treatment of gynaecological malignancies has progressed in two directions: reduction of the invasiveness of the surgery and expansion of the number and type of procedures performed. Gynaecological oncology focuses on the pelvis to the upper abdomen and the thorax to target (all visible disease) the last cancer cell in women with advanced ovarian cancer. Minimal-access surgery has evolved to include any operation by laparoscopy. It uses fewer ports (single-port surgery), and robotic assistance improves the comfort of the surgeon. The concept of fertility-sparing surgery for women with cervical cancer is now supported by mature data. The indication and the aggressiveness of the exenterative surgery are also broader than originally recommended. The ideal timing of surgery is under investigation in several areas, mainly in women with ovarian and cervical cancer. The aim is to reduce morbidity and mortality of surgical procedures while maintaining the survival outcome.


A Study Examining Compliance with the Anti-Tobacco Law Nb. 4207 Inside Taxis.
This observational study assessed compliance with the anti-tobacco Law Nb 4207 with regard to taxis in Çankaya district, Ankara. This descriptive study was conducted in Kızılay, Kuğulu, and Tandoğan intersections on January 18-23, 2016 between 9.00-11.00 and 14.00-16.00 hours in Ankara. Data regarding the status of the taxi (either cruising or not), smoking inside taxis, smoking status of the taxi drivers and/or clients, location of the clients in the taxi, presence of a child in the taxi, and status of the windows (open or not) were recorded using a data-gathering form. Three thousand six hundred fifty-six taxis were evaluated, of which 79 (2.2%) taxi drivers were observed smoking. Clients were observed smoking in 17 taxis (1.3%). Ninety-four taxi drivers and/or clients (2.6%) were observed smoking. Taxi drivers smoked more frequently in the absence of a client. In addition, a smoking client influenced the taxi driver's smoking status (p<0.001). Violation of the anti-tobacco Law Nb 4207 was observed. In this regard, the number of inspections needs to be increased. Systematic training programs for the taxi drivers regarding the risks of tobacco should be a priority. Preventive studies concerning the hazards of passive smoking should be also conducted at a community level.


Studying Collective Human Decision Making and Creativity with Evolutionary Computation.
We report a summary of our interdisciplinary research project "Evolutionary Perspective on Collective Decision Making" that was conducted through close collaboration between computational, organizational, and social scientists at Binghamton University. We redefined collective human decision making and creativity as evolution of ecologies of ideas, where populations of ideas evolve via continual applications of evolutionary operators such as reproduction, recombination, mutation, selection, and migration of ideas, each conducted by participating humans. Based on this evolutionary perspective, we generated hypotheses about collective human decision making, using agent-based computer simulations. The hypotheses were then tested through several experiments with real human subjects. Throughout this project, we utilized evolutionary computation (EC) in non-traditional ways-(1) as a theoretical framework for reinterpreting the dynamics of idea generation and selection, (2) as a computational simulation model of collective human decision-making processes, and (3) as a research tool for collecting high-resolution experimental data on actual collaborative design and decision making from human subjects. We believe our work demonstrates untapped potential of EC for interdisciplinary research involving human and social dynamics.


An algorithm for score aggregation over causal biological networks based on random walk sampling.
We recently published in BMC Systems Biology an approach for calculating the perturbation amplitudes of causal network models by integrating gene differential expression data. This approach relies on the process of score aggregation, which combines the perturbations at the level of the individual network nodes into a global measure that quantifies the perturbation of the network as a whole. Such "bottom-up" aggregation relates the changes in molecular entities measured by omics technologies to systems-level phenotypes. However, the aggregation method we used is limited to a specific class of causal network models called "causally consistent", which is equivalent to the notion of balance of a signed graph used in graph theory. As a consequence of this limitation, our aggregation method cannot be used in the many relevant cases involving "causally inconsistent" network models such as those containing negative feedbacks. In this note, we propose an algorithm called "sampling of spanning trees" (SST) that extends our published aggregation method to causally inconsistent network models by replacing the signed relationships between the network nodes by an appropriate continuous measure. The SST algorithm is based on spanning trees, which are a particular class of subgraphs used in graph theory, and on a sampling procedure leveraging the properties of specific random walks on the graph. This algorithm is applied to several cases of biological interest. The SST algorithm provides a practical means of aggregating nodal values over causally inconsistent network models based on solid mathematical foundations. We showed its utility in systems biology, where the nodal values can be perturbation amplitudes of protein activities or gene differential expressions, while the networks can be models of cellular signaling or expression regulation. Since the SST algorithm is based on general graph-theoretical considerations, it is scalable to arbitrary graph sizes and can potentially be used for performing quantitative analyses in any context involving signed graphs.


Cesarean section and chronic immune disorders.
Immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have shown a parallel increase in prevalence during recent decades in westernized countries. The rate of cesarean delivery has also increased in this period and has been associated with the development of some of these diseases. Mature children born by cesarean delivery were analyzed for risk of hospital contact for chronic immune diseases recorded in the Danish national registries in the 35-year period 1977-2012. Two million term children participated in the primary analysis. We studied childhood diseases with a suspected relation to a deviant immune-maturation and a debut at young age. The effect of cesarean delivery on childhood disease incidences were estimated by means of confounder-adjusted incidence rate ratios with 95% confidence intervals obtained in Poisson regression analyses. Children delivered by cesarean delivery had significantly increased risk of asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies, and leukemia. No associations were found between cesarean delivery and type 1 diabetes, psoriasis, or celiac disease. Cesarean delivery exemplifies a shared environmental risk factor in early life associating with several chronic immune diseases. Understanding commonalities in the underlying mechanisms behind chronic diseases may give novel insight into their origin and allow prevention.


Graphene/liquid crystal based terahertz phase shifters.
Due to its high electrical conductivity and excellent transmittance at terahertz frequencies, graphene is a promising candidate as transparent electrodes for terahertz devices. We demonstrate a liquid crystal based terahertz phase shifter with the graphene films as transparent electrodes. The maximum phase shift is 10.8 degree and the saturation voltage is 5 V with a 50 µm liquid crystal cell. The transmittance at terahertz frequencies and electrical conductivity depending on the number of graphene layer are also investigated. The proposed phase shifter provides a continuous tunability, fully electrical controllability, and low DC voltage operation.


Orientation selectivity of synaptic potentials in neurons of cat primary visual cortex.
Neurons of the visual cortex of the cat were penetrated with intracellular electrodes and postsynaptic potentials evoked by visual stimuli recorded. By alternately polarizing the cell with steady current injected through the recording electrode, IPSPs and EPSPs could be recorded and analyzed independently. Hyperpolarizing current suppressed IPSPs and enhanced EPSPs by moving the membrane potential toward the IPSP equilibrium potential. Depolarizing the cell toward the EPSP equilibrium potential enhanced IPSP. The responses to electrical stimulation of the LGN, where EPSPs and IPSPs could be distinguished easily by virtue of their characteristic latencies and shapes, were used to set the current injection to the appropriate level to view the two types of synaptic potential. EPSPs were found to be well oriented in that maximal depolarizing responses could be evoked at only one stimulus orientation; rotating the stimulus orientation in either direction produced a fall in the EPSP response. IPSPs were also well tuned to orientation, and invariably the preferred orientations of EPSPs and IPSPs in any one cell were identical. In addition, no systematic difference in the width of tuning of the two types of potential was seen. This result has been obtained from penetrations of over 30 cortical cells, including those with simple and complex receptive fields. It is concluded that orientation of cortical receptive fields is neither created nor sharpened by inhibition between neurons with different orientation preference. The function of inhibition evoked simultaneously with excitation by optimally oriented stimuli has yet to be determined, though it is likely to be the mechanism underlying other cortical receptive field properties, such as direction selectivity and end-stopping.


Single particle detection in CMOS compatible photonic crystal nanobeam cavities.
We report the label-free detection of single particles using photonic crystal nanobeam cavities fabricated in silicon-on-insulator platform, and embedded inside microfluidic channels fabricated in poly-dimethylsiloxane (PDMS). Our system operates in the telecommunication wavelength band, thus leveraging the widely available, robust and tunable telecom laser sources. Using this approach, we demonstrated the detection of polystyrene nanoparticles with dimensions down to 12.5nm in radius. Furthermore, binding events of a single streptavidin molecule have been observed.


Sexual experiences and quality of life in Turkish women using methods of contraception.
The aim of this study was to examine the sexual experiences and quality of life in women using methods of contraception. The sample of this descriptive study consisted of 259 women. The data were collected by the Personal Information Form, the Arizona Sexual Experiences Scale (ASES) and the World Health Organisation Quality of Life Scale (WHOQOL-BREF). It was found that 35.1% of the women use condoms, 30.1% of them use the Intrauterine Device (IUD), 22.0% had problems using the method and 39% had the side effects while using the method. There was a statistically significant difference between the state of having problems using the methods and quality of life average scores and between the state of having side effects and sexual life and quality of life average scores (p < .05). Impact statement What is already known on this subject? Sexual problems are common health problems among women and can lead to loss of self-esteem in women, depression and emotional stress. What do the results of this study add? Women who experience problems using a contraception method have a lower quality of life. Sexual dysfunctions were higher among those who experienced side effects of the methods, quality of life scores were lower. What are the implications of these findings for clinical practice and/or further research? Health professionals should provide information and counselling about possible problems or side effects and ways to cope with these problems or side effects.


A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging.
Task-induced deactivation (TID) refers to a regional decrease in blood flow during an active task relative to a "resting" or "passive" baseline. We tested the hypothesis that TID results from a reallocation of processing resources by parametrically manipulating task difficulty within three factors: target discriminability, stimulus presentation rate, and short-term memory load. Subjects performed an auditory target detection task during functional magnetic resonance imaging (fMRI), responding to a single target tone or, in the short-term memory load conditions, to target sequences. Seven task conditions (a common version and two additional levels for each of the three factors) were each alternated with "rest" in a block design. Analysis of covariance identified brain regions in which TID occurred. Analyses of variance identified seven regions (left anterior cingulate/superior frontal gyrus, left middle frontal gyrus, right anterior cingulate gyrus, left and right posterior cingulate gyrus, left posterior parieto-occipital cortex, and right precuneus) in which TID magnitude varied across task levels within a factor. Follow-up tests indicated that for each of the three factors, TID magnitude increased with task difficulty. These results suggest that TID represents reallocation of processing resources from areas in which TID occurs to areas involved in task performance. Short-term memory load and stimulus rate also predict suppression of spontaneous thought, and many of the brain areas showing TID have been linked with semantic processing, supporting claims that TID may be due in part to suspension of spontaneous semantic processes that occur during "rest" (Binder et al., 1999). The concept that the typical "resting state" is actually a condition characterized by rich cognitive activity has important implications for the design and analysis of neuroimaging studies.


Point- and frequency-specific response of the testicular artery to abdominal electroacupuncture in humans.
To clarify the role of the abdominal acupuncture points and the frequency of short-term electroacupuncture (EA) stimulation on testicular blood flow (TBF) in humans. A prospective, randomized study. University hospital, Department of Radiology, ultrasound unit. Eighty healthy male volunteers were randomly allocated to three groups in stage one and to a single group in stage two. In the first stage of the study, the abdominal acupuncture points ST-29 (guilai) were stimulated using simple needle insertion, 2 Hz burst EA or 10 Hz EA, in three different groups. In the second stage of the study, abdominal acupuncture points ST-25 (tianshu) were stimulated with the frequency found to be more effective in stage one. Stimulation was for 5 minutes in each group. Electroacupuncture and Doppler flowmeter. Four groups were compared for volume flow and other related parameters of TBF. The 10-Hz EA stimulation of ST-29 (guilai) increased TBF, but simple needle insertion and 2-Hz burst stimulation did not. The 10-Hz EA stimulation of ST-25 (tianshu) did not result in significant changes in TBF. For the first time point- and frequency-specific effects of abdominal EA on TBF are shown in humans. Further investigation is required to ascertain whether these findings may be helpful in the clinical treatment of infertile men.


Ubiquitin utilizes an acidic surface patch to alter chromatin structure.
Ubiquitylation of histone H2B, associated with gene activation, leads to chromatin decompaction through an unknown mechanism. We used a hydrogen-deuterium exchange strategy coupled with NMR spectroscopy to map the ubiquitin surface responsible for its structural effects on chromatin. Our studies revealed that a previously uncharacterized acidic patch on ubiquitin comprising residues Glu16 and Glu18 is essential for decompaction. These residues mediate promiscuous electrostatic interactions with the basic histone proteins, potentially positioning the ubiquitin moiety as a dynamic 'wedge' that prevents the intimate association of neighboring nucleosomes. Using two independent crosslinking strategies and an oligomerization assay, we also showed that ubiquitin-ubiquitin contacts occur in the chromatin environment and are important for the solubilization of the chromatin polymers. Our work highlights a novel, chromatin-related aspect of the 'ubiquitin code' and sheds light on how the information-rich ubiquitin modification can orchestrate different biochemical outcomes using distinct surface features.


A novel continuum-based framework for translating behavioral health integration to primary care settings.
Although evidence-based behavioral health integration models have been demonstrated to work well when implemented properly, primary care practices need practical guidance on the steps they can take to build behavioral health integration capacities. This is especially true for practice settings with fewer resources. This study is a pilot field test of a framework continuum composed of core components of behavioral health integration that can be used to translate the implementation of behavioral health into diverse clinical settings guided by a practice's priorities and available resources. This framework, in combination with technical assistance by the study team, was piloted in 11 small primary care sites (defined as ≤5 primary care providers) throughout New York State. Surveys were collected at baseline, 6 months, and 12 months. Informal check-in calls and site visits using qualitative semistructured individual and group interviews were conducted with 10 of the 11 sites. A mixed-methods approach was used to incorporate the survey data and qualitative thematic analysis. All practices advanced at least one level of behavioral health integration along various components of the framework. These advances included implementing depression screening, standardizing workflows for positive screens, integrating patient tracking tools for follow-up behavioral health visits, incorporating warm hand-offs to on-site or off-site behavioral health providers, and formalized external referrals using collaborative agreements. Practices reported they had overall positive experiences using the framework and offered feedback for how to improve future iterations. The framework continuum, in combination with technical assistance, was shown to be useful for primary care practices to advance integrated behavioral health care based on their priorities and resource availability. The results combined with feedback from the practices have yielded a revised "Framework 2.0" that includes a new organization as well as the addition of a "Sustainability" domain.


Limited degree-of-freedom adaptive optics and image reconstruction.
The use of limited degree-of-freedom adaptive optics in conjunction with statistical averaging and a linear image reconstruction algorithm is addressed. Image reconstruction is traded for full predetection compensation. It is shown through analytic calculations that the average optical transfer function (OTF) is significant for high spatial frequencies in the case of imaging through atmospheric turbulence with an adaptive optics system composed of a Hartmann-type wave-front sensor and a deformable mirror possessing far fewer actuators than one per atmospheric coherence diameter (r(0)). Statistical averaging is used to overcome the effects of measurement noise and randomness in individual realizations of the OTF. The imaging concept and signal-to-noise considerations are presented.


Lifestyle, dietary factors, and antibody levels to oral bacteria in cancer-free participants of a European cohort study.
Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked to several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria. Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunoglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured. IgG antibody levels were substantially lower among current and former smokers (1,697 and 1,677 ng/mL, respectively) than never smokers (1,960 ng/mL; p trend = 0.01), but did not vary by other factors, including body mass index, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country, and smoking status. The highest levels of total IgG were found among individuals with low education (2,419 ng/mL). Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria.


Rapid test for lung maturity, based on spectroscopy of gastric aspirate, predicted respiratory distress syndrome with high sensitivity.
Respiratory distress syndrome (RDS) is a major cause of mortality and morbidity in premature infants. By the time symptoms appear, it may already be too late to prevent a severe course, with bronchopulmonary dysplasia or mortality. We aimed to develop a rapid test of lung maturity for targeting surfactant supplementation. Concentrations of the most surface-active lung phospholipid dipalmitoylphosphatidylcholine and sphingomyelin in gastric aspirates from premature infants were measured by mass spectrometry and expressed as the lecithin/sphingomyelin ratio (L/S). The same aspirates were analysed with mid-infrared spectroscopy. Subsequently, L/S was measured in gastric aspirates and oropharyngeal secretions from another group of premature infants using spectroscopy and the results were compared with RDS development. The 10-minute analysis required 10 μL of aspirate. An L/S algorithm was developed based on 89 aspirates. Subsequently, gastric aspirates were sampled in 136 infants of 24-31 weeks of gestation and 61 (45%) developed RDS. The cut-off value of L/S was 2.2, sensitivity was 92%, and specificity was 73%. In 59 cases, the oropharyngeal secretions had less valid L/S than gastric aspirate results. Our rapid test for lung maturity, based on spectroscopy of gastric aspirate, predicted RDS with high sensitivity.


Genotoxicity of field-collected inter-tidal sediments from Cork Harbor, Ireland, to juvenile turbot (Scophthalmus maximus L.) as measured by the Comet assay.
The alkaline single cell gel electrophoresis (SCGE) or Comet assay was employed to test the potential of surficial sediment collected from Cork Harbor, Ireland, to induce DNA damage in turbot (Scophthalmus maximus L.) in a laboratory exposure experiment. Turbot were exposed for 21 days to field-collected sediment from Cork Harbor and from a relatively clean reference site at Ballymacoda and sampled at 0, 7, 14, and 21 days. As a positive control for the sediment exposure experiment, a subsample of the turbot was exposed to cadmium chloride-spiked seawater. DNA damage analysis was performed on epidermal, gill, spleen, liver, and whole blood cell preparations. Liver, gill, and blood were the most sensitive tissues while a lower level of damage was detected in the epidermis and spleen. The blood was determined to be a suitable predictor of DNA damage in the whole organism. Chemical analysis of the sediment indicated that polycyclic aromatic hydrocarbons formed the bulk of the contaminants, with the harbor sites having almost double the levels of those from the reference site. The data indicated that turbot exposed to sediments from Cork Harbor elicited a significant increase in DNA damage in comparison with those exposed to sediment from the reference site and that exposure to the contaminated sediments caused a multi-organ genotoxic response. Results from the study indicate a relationship between the presence of genotoxicants in sediment and DNA damage. This finding was encouraging with regard to the potential use of the Comet assay as part of a marine biomonitoring strategy.


Medical librarian 2.0.
Web 2.0 refers to an emerging social environment that uses various tools to create, aggregate, and share dynamic content in ways that are more creative and interactive than transactions previously conducted on the Internet. The extension of this social environment to libraries, sometimes called Library 2.0, has profound implications for how librarians will work, collaborate, and deliver content. Medical librarians can connect with present and future generations of users by learning more about the social dynamics of Web 2.0's vast ecosystem, and incorporating some of its interactive tools and technologies (tagging, peer production, and syndication) into routine library practice. doi: 10.1300/J115v26n01_01.


Autonomic dysregulation in burnout and depression: evidence for the central role of exhaustion.
Objectives Given the important role of the autonomic nervous system (ANS) in stress regulation, astonishingly little is known about ANS functioning in burnout, a condition arising after prolonged exposure to work-related stress. The current study sought to investigate ANS modulation, as indexed by vagally-mediated heart rate variability (HRV), in relation to burnout symptomatology to (i) distinguish associations between the three dimensions of burnout [emotional exhaustion (EE), cynicism, reduced personal accomplishment] and (ii) investigate overlap in associations with depressive symptomatology. Methods Assessments of vagally-mediated HRV (ie, root mean square of successive differences, RMSSD) were conducted in a large population-based sample from the Dresden Burnout Study [N=410, mean age 42.2, standard deviation (SD) 11.2 years; 33.4% male]. Vagally-mediated HRV was assessed for 90 seconds during an emotionally-arousing situation (venipuncture, recumbent), a 335-second recumbent recovery period, and a 335-second seated resting condition. Results Results from multiple linear regression analyses revealed that EE was negatively related to RMSSD during venipuncture (=β -0.11, P=0.03) and the seated rest (β= -0.09, P=0.04) even after accounting for established ANS modulators (eg, age, body mass index). This pattern was not observed for the other dimensions of burnout. Exploratory analyses of depressive symptomatology further revealed that RMSSD was significantly and inversely associated with burnout-related symptoms but not with the core criteria of depression (eg, depressed mood). Conclusions This study presents evidence for a link between exhaustion and reduced vagal function, both in burnout and depression, suggesting that ANS modulations may not be disorder-specific but rather a psychophysiological correlate of an underlying feature shared by both conditions.


Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers.
Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARγ binding, leading to the formation of PPARγ "superenhancers" that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARγ and appears to cooperate with PPARγ in a feed-forward manner to activate and maintain the brite-selective gene program.


Genome trees constructed using five different approaches suggest new major bacterial clades.
The availability of multiple complete genome sequences from diverse taxa prompts the development of new phylogenetic approaches, which attempt to incorporate information derived from comparative analysis of complete gene sets or large subsets thereof. Such attempts are particularly relevant because of the major role of horizontal gene transfer and lineage-specific gene loss, at least in the evolution of prokaryotes. Five largely independent approaches were employed to construct trees for completely sequenced bacterial and archaeal genomes: i) presence-absence of genomes in clusters of orthologous genes; ii) conservation of local gene order (gene pairs) among prokaryotic genomes; iii) parameters of identity distribution for probable orthologs; iv) analysis of concatenated alignments of ribosomal proteins; v) comparison of trees constructed for multiple protein families. All constructed trees support the separation of the two primary prokaryotic domains, bacteria and archaea, as well as some terminal bifurcations within the bacterial and archaeal domains. Beyond these obvious groupings, the trees made with different methods appeared to differ substantially in terms of the relative contributions of phylogenetic relationships and similarities in gene repertoires caused by similar life styles and horizontal gene transfer to the tree topology. The trees based on presence-absence of genomes in orthologous clusters and the trees based on conserved gene pairs appear to be strongly affected by gene loss and horizontal gene transfer. The trees based on identity distributions for orthologs and particularly the tree made of concatenated ribosomal protein sequences seemed to carry a stronger phylogenetic signal. The latter tree supported three potential high-level bacterial clades,: i) Chlamydia-Spirochetes, ii) Thermotogales-Aquificales (bacterial hyperthermophiles), and ii) Actinomycetes-Deinococcales-Cyanobacteria. The latter group also appeared to join the low-GC Gram-positive bacteria at a deeper tree node. These new groupings of bacteria were supported by the analysis of alternative topologies in the concatenated ribosomal protein tree using the Kishino-Hasegawa test and by a census of the topologies of 132 individual groups of orthologous proteins. Additionally, the results of this analysis put into question the sister-group relationship between the two major archaeal groups, Euryarchaeota and Crenarchaeota, and suggest instead that Euryarchaeota might be a paraphyletic group with respect to Crenarchaeota. We conclude that, the extensive horizontal gene flow and lineage-specific gene loss notwithstanding, extension of phylogenetic analysis to the genome scale has the potential of uncovering deep evolutionary relationships between prokaryotic lineages.


Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.
The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not.


Recruiting unmotivated smokers into a smoking induction trial.
Little is known about effective methods to recruit unmotivated smokers into cessation induction trials, the reasons unmotivated smokers agree to participate, and the impact of those reasons on study outcomes. A mixed-method approach was used to examine recruitment data from a randomized controlled cessation induction trial that enrolled 255 adult smokers with low motivation to quit. Over 15 months, 33% of smokers who inquired about the study were enrolled. Common recruitment methods included word-of-mouth, print advertisements and clinic referrals. Frequently mentioned reasons for participating included to: gain financial incentives (44.7%), learn about research or help others quit (43%), learn about smoking and risks (40%) and help with future quits (i.e. Quit Assistance, 23.9%). Separate regression models predicting study outcomes at 26 weeks indicated that smokers who said they participated for Quit Assistance reported higher motivation to quit (B 1.26) and were more likely to have made a quit attempt (OR 2.03) compared to those not mentioning this reason, when baseline characteristics were controlled. Understanding reasons for unmotivated smokers' interest in treatment can help practitioners and researchers design effective strategies to engage this population.


Early diagnosis of ventriculoperitoneal shunt infections and malfunctions in children with hydrocephalus.
This retrospective study assessed the parameters of ventriculoperitoneal shunt infection and malfunction found in 129 children with hydrocephalus who had undergone a ventriculoperitoneal shunt placement at Taipei Veterans General Hospital from January 1997 to June 2001. The clinical characteristics and differences among these patients were reviewed to determine the potential predictors of shunt infection and malfunction. Fever (60%, 6/ 10) and seizure (40%, 4/10) occurred significantly more often in the infection group than in the malfunction and control groups (p < 0.05). A higher blood C-reactive protein level was noted in the infection group than in the malfunction and control groups (p < 0.05). Examination of the cerebrospinal fluid of infected patients showed significantly higher white blood cell count and neutrophil count, higher protein concentration, and lower glucose levels compared with the other 2 groups (p < 0.05). However, the number of patients with cerebrospinal fluid eosinophilia was significantly higher in the malfunction group (p < 0.05). The diagnostic usefulness of laboratory parameters in patients with ventriculoperitoneal shunt infection is as follow: cerebrospinal fluid white blood cell count over 100/mm3, 96% specificity and a positive predictive value of 0.55; and cerebrospinal fluid neutrophils over 10%, 90% sensitivity and a negative predictive value of 0.99. In conclusion, Fever, seizure, high blood C-reactive protein, combined with leukocytosis, neutrophil over 10%, low glucose level, and high protein level in the ventricular fluid are factors that may help in distinguishing shunt infection from shunt malfunction.


A novel function for a ubiquitous plant enzyme pectin methylesterase: the host-cell receptor for the tobacco mosaic virus movement protein.
Plant virus-encoded movement proteins promote viral spread between plant cells via plasmodesmata. The movement is assumed to require a plasmodesmata targeting signal to interact with still unidentified host factors presumably located on plasmodesmata and cell walls. The present work indicates that a ubiquitous cell wall-associated plant enzyme pectin methylesterase of Nicotiana tabacum L. specifically binds to the movement protein encoded by tobacco mosaic virus. We also show that pectin methylesterase is an RNA binding protein. These data suggest that pectin methylesterase is a host cell receptor involved in cell-to-cell movement of tobacco mosaic virus.


Shiftwork, job type, and the work environment as joint predictors of health-related outcomes.
This article examines the potential confounding of observed relations between shiftwork and health outcomes by differences in the jobs typically carried out by shiftworkers and dayworkers. Objective factors (daywork vs. day/night shiftwork and job type) and work perceptions (job demand, discretion, social support, and physical stressors) were analyzed as joint predictors of psychosomatic complaints (headaches and musculoskeletal, gastric, and sleep problems), affective distress, and work-related injuries in data from oil industry personnel (N = 1,462). Logistic regression showed that, after control for individual differences (including age and negative affectivity), shiftwork and job type each predicted specific health outcomes when evaluated simultaneously. Work perceptions also contributed significantly to each outcome, partially mediating relations between job type and health.


First Report of Spot Form Net Blotch Caused by Pyrenophora teres f. maculata on Barley in the Mon-Dak Area of the United States.
Pyrenophora teres Drechs. causes net blotch of barley, a common foliar disease in cultivation zones around the world. The disease occurs in two forms, namely a net form net blotch (NFNB) caused by P. teres f. teres and a spot form net blotch (SFNB) caused by P. teres f. maculata. As in other parts of the northern Great Plains, in the Mon-Dak area (western North Dakota and eastern Montana), NFNB is prevalent. SFNB was first reported in western Montana in 1983 (1) and more recently in eastern North Dakota in 2010 (3) but not in the Mon-Dak area. In the summer of 2011, unusual spot lesions that were surrounded by necrosis or chlorosis were observed on different barley cultivars in fields at Williston, ND, Nesson Valley, ND, and Sidney, MT areas. Diseased leaves from various barley cvs. from the three locations were transferred to water agar and incubated at room temperature for 24 h to induce sporulation. Morphological examination of conidia (45 to 169 × 15 to 21 μm) did not show significant differences from a known isolate of P. teres f. teres 0-1 (provided by Tim Friesen, ARS, Fargo, ND). For pathogenicity testing, six 14-day-old plants of barley cv. Tradition were sprayed until runoff with a 2,000 spore/ml suspension of two isolates from each location and the control P. teres f. maculata isolate DEN2.6 (provided by Tim Friesen). Plants were incubated first in a lighted humidity chamber for 24 h and then in a greenhouse for 7 days at 21°C. Regardless of inoculum source, spot lesions surrounded by necrosis or chlorosis, typical of SFNB, appeared on the inoculated leaves within 7 days. Fungi isolated from symptomatic leaves were identified as P. teres and the morphology of the conidia was undistinguishable from those of P. teres f. teres. All control plants which were sprayed with sterile distilled water were symptomless. The pathogenicity test was repeated. Rapid PCR detection and amplicon sequencing (2) of the internal transcribed spacer (ITS) region of ribosomal genes was performed on field and pathogenicity test leaf lesion samples to confirm the presence of P. teres f. maculata. DNA templates were prepared using the Extract-N-Amp Plant PCR Kits (Sigma Chemical Co., St. Louis, MO) and subjected to PCR using ITS1 and ITS4 primers. Amplicons were then purified and sequenced. The 585-bp nucleotide sequences of P. teres f. maculata from Mon-Dak area were submitted to GenBank under accession nos. PtmNES1 (JX187587), PtmSDY1 (JX187588), PtmSDY2 (JX187589), and PtmWIL1 (JX187590). The sequences from the four locations shared 100% similarity and also with P. teres f. maculata (EF452471) from GenBank while showing 10 nucleotide differences (99% similarity) with P. teres f. teres (EF452472).The results represent first report of SFNB in the Mon-Dak. Barley is one of the most important crops in the area. Resistance of the NFNB and SFNB of barley are controlled by different genes (4). Based on this report, SFNB therefore have to be considered in selection of barley cultivars for cultivation in the area. References: (1) H. E Bockelman et al. Plant Dis. 67:696, 1983. (2) R. T. Lartey et al. J. Sugar Beet Res. 40:1, 2003. (3) Z. H. Liu and T. L. Friesen. Plant Dis. 94:480, 2010. (4) O. M. Manninen et al. Genome. 46:1564, 2006.