Using standardized survey items with older adults hospitalized for chronic illness.
We used the stages of the question response model as a framework to discuss the challenges in administering standardized measures to older adults hospitalized with chronic illnesses. Items with complex content and those with negative stems were associated with difficulties during the comprehension stage. Present experience with the subject of the item was a barrier to retrieving past experiences. The lack of relevance of an item's content to the respondent's situation was associated with problems during the judgment stage. The numeric response format of the items was an obstacle during the response stage. Strategies to enhance the validity of the surveys included breaking up, rephrasing, and contextualizing items, and using descriptive response options.


[Host range of drosophila melanogaster C virus among diptera and lepidoptera (author's transl)].
The host range of the C picornavirus of Drosophila melanogaster was studied, using numerous strains of Drosophila together with four other genera of diptera and two species of lepidoptera. C virus was injected into the different hosts and serially passaged in them. The extracts from each passage were biologically assayed on virus free D. melanogaster. Four different situations were found. 1) A high level of multiplication leading, in 45 strains of Drosophilidae, to the early death of the hosts. This phenomenon was particularly related to the subgroup melanogaster and in the dipteron Ceratitis capitata. The titre of the virus in this latter insect was high as in D. melanogaster, but its cellular tropism was wider. 2) An active viral multiplication but without symptoms, in two strains of D. immigrans and in the lepidopteron Galleria mellonella. In these two insects, the viral titre was clearly inferior to that observed in D. melanogaster. 3) Maintenance of the virus, without multiplication in the dipteron Calliphora erythrocephala and the lepidopteron Arctia caja. In these insects, the decrease in virus titre was directly related to the dilution factor at each passage. 4) Rapid disappearance of the virus, in the mosquitoes Culex pipiens and Aedes aegypti. The host range of C virus is compared to that of Sigma virus of Drosophila and of two other picornaviruses of insects.


Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations.
Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration.


Using dense locality sampling resolves the subtle genetic population structure of the dispersive fish species Plecoglossus altivelis.
In dispersive species with continuous distributions, genetic differentiation between local populations is often absent or subtle and thus difficult to detect. To incorporate such subtle differentiation into management plans, it may be essential to analyse many samples from many localities using adequate numbers of high-resolution genetic markers. Here, we evaluated the usefulness of dense locality sampling in resolving genetic population structure in the ayu (Plecoglossus altivelis), a dispersive fish important in Japanese inland fisheries. Genetic variability in, and differentiation between, ayu populations around the Japan-Ryukyu Archipelago were investigated in 4746 individuals collected from 120 localities by genotyping 12 microsatellite markers. These individuals represented the two subspecies of ayu, namely the Ryukyuan subspecies (Plecoglossus altivelis ryukyuensis) and both amphidromous and landlocked forms of the nominotypical subspecies (P. a. altivelis) along the archipelago. We successfully detected an absence of genetic differentiation within the landlocked form and subtle but significant differentiation and clear geographic patterns of genetic variation among populations of the amphidromous form, which had been considered genetically homogeneous. This suggests that dense locality sampling effectively resolves subtle differences in genetic population structure, reducing stochastic deviation in the detection of genetic differentiation and geographic patterns in local populations of this dispersive species. Resampling analyses based on empirical data sets clearly demonstrate the effectiveness of increasing the number of locality samples for stable and reliable estimations of genetic fixation indices. The genetic population structure observed within the amphidromous form provides useful information for identifying management or conservation units in ayu.


Propagation loss spectroscopy on single nanowire active waveguides.
A new technique is reported where by combining spatially and spectrally resolved scanning optical microscopy on single nanowire active waveguides, waveguide propagation loss and dispersion can be determined. The waveguide propagation loss spectra have been utilized to obtain insights into the optical absorption spectra of these unique nanostructured materials, which are modified in comparison to bulk materials. The propagation spectra and waveguide dispersion show clear signatures of electronic effects such as exciton-polariton formation. These results show the importance of the polaritonic nature of waveguiding in semiconducting nanoscale optical cavities and provide insights for the integration of semiconductor nanowire waveguides in nanophotonic circuitry.


A note on dealing with missing standard errors in meta-analyses of continuous outcome measures in WinBUGS.
A meta-analysis of a continuous outcome measure may involve missing standard errors. This is not a problem depending on assumptions made about the population standard deviation. Multiple imputation can be used to impute missing values while allowing for uncertainty in the imputation. Markov chain Monte Carlo simulation is a multiple imputation technique for generating posterior predictive distributions for missing data. We present an example of imputing missing variances using WinBUGS. The example highlights the importance of checking model assumptions, whether for missing or observed data.


A self-amplifying nanodrug to manipulate the Janus-faced nature of ferroptosis for tumor therapy.
Ferroptosis, an unusual non-apoptotic cell death caused by the iron-dependent accumulation of lipid peroxide, enables the flexible design of an antitumor platform. Specifically, as a positive role, ferroptosis can induce an immune response accompanied with the interferon-γ (IFN-γ)-triggered disruption of the glutathione peroxidase 4 pathway for cascade enhancement of ferroptotic cell death and ferroptosis-induced immunotherapeutic efficacy. However, as a negative role, ferroptosis also triggers inflammation-associated immunosuppression by up-regulation of the cyclooxygenase-2/prostaglandin E2 pathway and IFN-γ-associated adaptive immune resistance by up-regulation of programmed death ligand-1 (PD-L1), impeding the antitumor efficacy of multiple immune cells by immune escape. Negative and positive roles endow ferroptosis with a Janus-faced nature. It is urgent to manipulate the Janus-faced nature of ferroptosis for eliciting the maximized ferroptotic therapeutic efficacy. Herein, a self-amplifying nanodrug (RCH NPs) was designed by co-assembling hemin (ferric porphyrin), celecoxib (anti-inflammatory drug) and roscovitine (cyclin-dependent kinase 5 inhibitor) with the assistance of human serum albumin for reprograming the Janus-faced nature of ferroptosis. During hemin-triggered ferroptosis, celecoxib disrupted the inflammation-related immunosuppression while roscovitine destroyed the IFN-γ-induced up-regulation of PD-L1 via the genetic blockade effect. The RCH NPs thus demonstrated superior therapeutic effects on tumors, thanks to self-amplifying ferroptotic immunotherapy. Our work offers a conceptually innovative strategy for harnessing ferroptosis against tumors.


Is Chickpea a Potential Substitute for Soybean? Phenolic Bioactives and Potential Health Benefits.
Legume seeds are rich sources of protein, fiber, and minerals. In addition, their phenolic compounds as secondary metabolites render health benefits beyond basic nutrition. Lowering apolipoprotein B secretion from HepG2 cells and decreasing the level of low-density lipoprotein (LDL)-cholesterol oxidation are mechanisms related to the prevention of cardiovascular diseases (CVD). Likewise, low-level chronic inflammation and related disorders of the immune system are clinical predictors of cardiovascular pathology. Furthermore, DNA-damage signaling and repair are crucial pathways to the etiology of human cancers. Along CVD and cancer, the prevalence of obesity and diabetes is constantly increasing. Screening the ability of polyphenols in inactivating digestive enzymes is a good option in pre-clinical studies. In addition, in vivo studies support the role of polyphenols in the prevention and/or management of diabetes and obesity. Soybean, a well-recognized source of phenolic isoflavones, exerts health benefits by decreasing oxidative stress and inflammation related to the above-mentioned chronic ailments. Similar to soybeans, chickpeas are good sources of nutrients and phenolic compounds, especially isoflavones. This review summarizes the potential of chickpea as a substitute for soybean in terms of health beneficial outcomes. Therefore, this contribution may guide the industry in manufacturing functional foods and/or ingredients by using an undervalued feedstock.


Method to protect charge recombination in the back-contact dye-sensitized solar cell.
We prepared a back-contact dye-sensitized solar cell and investigated effect of the sputter deposited thin TiO₂ film on the back-contact ITO electrode on photovoltaic property. The nanocrystalline TiO₂ layer with thickness of about 11 μm formed on a plain glass substrate in the back-contact structure showed higher optical transmittance than that formed on an ITO-coated glass substrate, which led to an improved photocurrent density by about 6.3%. However, photovoltage was found to decrease from 817 mV to 773 mV. The photovoltage recovered after deposition of a 35 nm-thick thin TiO₂ film on the surface of the back-contact ITO electrode. Little difference in time constant for electron transport was found for the back-contact ITO electrodes with and without the sputter deposited thin TiO₂ film. Whereas, time constant for charge recombination increased after introduction of the thin TiO₂ film, indicating that such a thin TiO₂ film protected back electron transfer, associated with the recovery of photovoltage. As the result of the improved photocurrent density without deterioration of photovoltage, the back-contact dye-sensitized solar cell exhibited 13.6% higher efficiency than the ITO-coated glass substrate-based dye-sensitized solar cell.


Learning to Model G-Quadruplexes: Current Methods and Perspectives.
G-quadruplexes have raised considerable interest during the past years for the development of therapies against cancer. These noncanonical structures of DNA may be found in telomeres and/or oncogene promoters, and it has been observed that the stabilization of such G-quadruplexes may disturb tumor cell growth. Nevertheless, the mechanisms leading to folding and stabilization of these G-quadruplexes are still not well established, and they are the focus of much current work in this field. In seminal works, stabilization was observed to be produced by cations. However, subsequent studies showed that different kinds of small molecules, from planar and nonplanar organic molecules to square-planar and octahedral metal complexes, may also lead to the stabilization of G-quadruplexes. Thus, the comprehension and rationalization of the interaction of these small molecules with G-quadruplexes are also important topics of current interest in medical applications. To shed light on the questions arising from the literature on the formation of G-quadruplexes, their stabilization, and their interaction with small molecules, synergies between experimental studies and computational works are needed. In this review, we mainly focus on in silico approaches and provide a broad compilation of different leading studies carried out to date by different computational methods. We divide these methods into twomain categories: (a) classical methods, which allow for long-timescale molecular dynamics simulations and the corresponding analysis of dynamical information, and (b) quantum methods (semiempirical, quantum mechanics/molecular mechanics, and density functional theory methods), which allow for the explicit simulation of the electronic structure of the system but, in general, are not capable of being used in long-timescale molecular dynamics simulations and, therefore, give a more static picture of the relevant processes.


Hexose monophosphate shunt activity in erythrocytes related to cell age.
Erythrocytes were separated by age using a combination of density centrifugation and counterflow centrifugation and tested for basal activity of the hexose monophosphate shunt (HMP-shunt) as well as the methylene blue-stimulated maximal capacity by measuring CO2 production. No significant differences were found in basal HMP-shunt activity, but the maximal methylene blue-stimulated activity of old erythrocytes reached only half of the activity of the total cell population. The maximal HMP-shunt activity showed a significant correlation with hexokinase activity, but not with glucose-6-phosphate dehydrogenase activity in all but the youngest cells. The sensitivity to oxidative stress was tested by measuring the kinetics of pyruvate kinase isolated from erythrocytes incubated in presence and absence of methylene blue. Pyruvate kinase kinetics were affected more in the old cell population than in the total cell population: the K0.5 for phosphoenol-pyruvate increased four times in the unseparated cells and eight times in old cells.


Binding of sFRP-3 to EGF in the extra-cellular space affects proliferation, differentiation and morphogenetic events regulated by the two molecules.
sFRP-3 is a soluble antagonist of Wnts, widely expressed in developing embryos. The Wnt gene family comprises cysteine-rich secreted ligands that regulate cell proliferation, differentiation, organogenesis and oncogenesis of different organisms ranging from worms to mammals. In the canonical signal transduction pathway Wnt proteins bind to the extracellular domain of Frizzled receptors and consequently recruit Dishevelled (Dsh) to the cell membrane. In addition to Wnt membrane receptors belonging to the Frizzled family, several other molecules have been described which share homology in the CRD domain and lack the putative trans-membrane domain, such as sFRP molecules (soluble Frizzled Related Protein). Among them, sFRP-3 was originally isolated from bovine articular cartilage and also as a component of the Spemann organizer. sFRP-3 blocks Wnt-8 induced axis duplication in Xenopus embryos and binds to the surface of cells expressing a membrane-anchored form of Wnt-1. Injection of sFRP-3 mRNA blocks expression of XMyoD mRNA and leads to embryos with enlarged heads and shortened trunks. Here we report that sFRP-3 specifically blocks EGF-induced fibroblast proliferation and foci formation. Over-expression of sFRP-3 reverts EGF-mediated inhibition of hair follicle development in the mouse ectoderm while its ablation in Xenopus maintains EGF-mediated inhibition of ectoderm differentiation. Conversely, over-expression of EGF reverts the inhibition of somitic myogenesis and axis truncation in Xenopus and mouse embryos caused by sFRP-3. In vitro experiments demonstrated a direct binding of EGF to sFRP-3 both on heparin and on the surface of CHO cells where the molecule had been membrane anchored. sFRP-3 and EGF reciprocally inhibit their effects on cell proliferation, differentiation and morphogenesis and indeed are expressed in contiguous domains of the embryo, suggesting that in addition to their canonical ligands (Wnt and EGF receptor, respectively) these molecules bind to each other and regulate their activities during embryogenesis.


Preparation of biodegradable polycaprolactone/poly (ethylene glycol)/polycaprolactone (PCEC) nanoparticles.
Biodegradable polyetherester copolymer (PCL/PEG/PCL, PCEC) was synthesized by ring-opening polymerization of epsilon-caprolactone initiated by poly(ethylene glycol) (PEG). The PCEC nanoparticles were prepared by solvent diffusion method or w/o/w double emulsion method. The obtained particles' morphology was observed on scanning electron microscopy, and the particle size distribution was determined using Malvern laser particle sizer. Bovine serum albumin was used as the model water-soluble protein drug, which was successfully encapsulated in PCEC nanoparticles, the drug release behavior was studied in detail. The hydrolytic degradation behavior of the PCEC nanoparticles was also studied.


Pulmonary hypertension and right heart dysfunction in chronic lung disease.
Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.


Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal-Embryo Communication.
Embryo implantation into maternal endometrium is critical for initiation and establishment of pregnancy, requiring developmental synchrony between endometrium and blastocyst. However, factors regulating human endometrial-embryo cross talk and facilitate implantation remain largely unknown. Extracellular vesicles (EVs) are emerging as important mediators of this process. Here, a trophectoderm spheroid-based in vitro model mimicking the pre-implantation human embryo is used to recapitulate important functional aspects of blastocyst implantation. Functionally, human endometrial EVs, derived from hormonally treated cells synchronous with implantation, are readily internalized by trophectoderm cells, regulating adhesive and invasive capacity of human trophectoderm spheroids. To gain molecular insights into mechanisms underpinning endometrial EV-mediated enhancement of implantation, quantitative proteomics reveal critical alterations in trophectoderm cellular adhesion networks (cell adhesion molecule binding, cell-cell adhesion mediator activity, and cell adherens junctions) and metabolic and gene expression networks, and the soluble secretome from human trophectodermal spheroids. Importantly, transfer of endometrial EV cargo proteins to trophectoderm to mediate changes in trophectoderm function is demonstrated. This is highlighted by correlation among endometrial EVs, the trophectodermal proteome following EV uptake, and EV-mediated trophectodermal cellular proteome, important for implantation. This work provides an understanding into molecular mechanisms of endometrial EV-mediated regulation of human trophectoderm functions-fundamental in understanding human endometrium-embryo signaling during implantation.


Family History and Risk of Renal Cell Carcinoma: A National Multiregister Case-Control Study.
Our purpose was to investigate the association between family history of renal cell carcinoma (RCC) and RCC risk. RCC cases diagnosed in Sweden between 2005 and 2014 and 10 matched controls were identified using the Renal Cell Cancer Database Sweden, with linkage to the Multigeneration Register and the Swedish Cancer Registry. The association between a family history of RCC and RCC was investigated, overall and by sex and age groups. Among 9416 RCC cases, 294 (3.1%) had 1 or more parent or sibling (first-degree relative [FDR]) with RCC. Median age at diagnosis for cases with an affected FDR was 65 years (IQR 59-71) and 68 years (IQR 60-75) for all cases. The proportion of women was significantly higher among familial RCC compared to sporadic RCC (44.6% vs 38.5%, P = .035). RCC was twice as likely with 1 or more FDR with RCC (OR 1.9; CI 1.65-2.16). Stratified analysis showed an OR of 2.4 for women (CI 1.93-2.92) and 1.6 for men (CI 1.35-1.93). Two or more FDRs was associated with a sixfold increased risk (95% CI 2.37-15.5). Familial RCC was strongly associated with bilateral and multifocal tumors (OR 5.5; CI 2.36-13.0, OR 3.5; CI 1.89-6.49). In this Swedish data set, 3.1% of RCC patients have 1 or more FDR diagnosed with RCC. There was no statistical difference in median age between sporadic RCC and familial RCC. Having 1 or more FDR with RCC approximately doubles the risk of RCC with a higher risk increase for women than for men. People with 2 FDRs with RCC constitute a small high-risk group that may benefit from screening.


H19 promotes endometrial cancer progression by modulating epithelial-mesenchymal transition.
Endometrial cancer is one of the most common types of gynecological malignancy worldwide. Novel biomarkers and therapeutic targets are imperative for improving patients' survival. Previous studies have suggested the long non-coding RNA H19 as a potential cancer biomarker. To investigate the role of H19 in endometrial cancer, the present study examined the expression pattern of H19 in endometrial cancer tissues by quantitative polymerase chain reaction, and characterized its function in the endometrial cancer cell line via knocking down its expression with small interfering RNAs. It was found that H19 level was significantly higher in tumor tissues than in paratumoral tissues. Knockdown of H19 did not affect the growth rate of HEC-1-B endometrial cancer cells, but significantly suppressed in vitro migration and invasion of HEC-1-B cells. Furthermore, H19 downregulation decreased Snail level and increased E-cadherin expression without affecting vimentin level, indicating partial reversion of epithelial-mesenchymal transition (EMT). The present findings suggested that H19 contributed to the aggressiveness of endometrial cancer by modulating EMT process.


Frequency of pubic hair transfer during sexual intercourse.
This study measured the frequency of pubic hair transfer between a limited number of consenting heterosexual partners. The results derive from controlled experiments with a number of human subjects rather than forensic casework. Standardized collection procedures were observed, situational variables were tracked. Participants (forensic laboratory employees and their spouses) were six Caucasian couples who collected their pubic hair combings immediately following intercourse. Subjects provided informed consent in accordance with the protocol for human subjects approved by the U.A.B. institutional review board. The experiment was replicated ten times for five couples, and five times for another couple (total n = 110). Transfer frequencies were calculated from instances where foreign (exogenous) hairs were observed. Results showed at least one exogenous pubic hair in 17.3% (19/110) of combings. Transfers to males (23.6%, or 13/55) were more prevalent than transfers to females (10.9%, or 6/55). Only once were transfers observed simultaneously between both male and female. A total of 28 exogenous pubic hairs were identified. Subjects reported intercourse duration of 2-25 min, intervening intervals of 1-240 h, pre-coital bathing intervals of 0.25-24 h, and predominantly missionary position (76%). No clear relationship among these other survey variables was observed. The prevalence of female-to-male pubic hair transfers suggests the importance of collecting pubic hair combings from the male suspects as well as from female victims, provided the time interval is not extreme. Even under these optimum collection conditions, pubic hair transfers were observed only 17.3% of the time.


Standing Up for Learning: A Pilot Investigation on the Neurocognitive Benefits of Stand-Biased School Desks.
Standing desks have proven to be effective and viable solutions to combat sedentary behavior among children during the school day in studies around the world. However, little is known regarding the potential of such interventions on cognitive outcomes in children over time. The purpose of this pilot study was to determine the neurocognitive benefits, i.e., improvements in executive functioning and working memory, of stand-biased desks and explore any associated changes in frontal brain function. 34 freshman high school students were recruited for neurocognitive testing at two time points during the school year: (1) in the fall semester and (2) in the spring semester (after 27.57 (1.63) weeks of continued exposure). Executive function and working memory was evaluated using a computerized neurocognitive test battery, and brain activation patterns of the prefrontal cortex were obtained using functional near infrared spectroscopy. Continued utilization of the stand-biased desks was associated with significant improvements in executive function and working memory capabilities. Changes in corresponding brain activation patterns were also observed. These findings provide the first preliminary evidence on the neurocognitive benefits of standing desks, which to date have focused largely on energy expenditure. Findings obtained here can drive future research with larger samples and multiple schools, with comparison groups that may in turn implicate the importance of stand-biased desks, as simple environmental changes in classrooms, on enhancing children's cognitive functioning that drive their cognitive development and impact educational outcomes.


Graphene-Based Nanomaterials and Their Interactions with Lipid Membranes.
Graphene-based nanomaterials (GNMs) have captured increasing attention in the recent advancement of materials science and nanotechnology owing to their excellent physicochemical properties. Despite having unquestionable advances, the application of GNMs in biological and medical sciences is still limited due to the lack of knowledge and precise control over their interaction with the biological milieu. The cellular membrane is the first barrier with which GNMs interact before entering a cell. Therefore, understanding how they interact with cell membranes is important from the perspective of safe use in biological and biomedical fields. In this review, we systematically summarize the recent efforts in predicting the interactions between GNMs and model cellular membranes. This review provides insights into how GNMs interact with lipid membranes and self-assemble in and around them. Both the computational simulations and experimental observations are summarized. The interactions are classified depending on the physicochemical properties (structure, chemistry, and orientation) of GNMs and various model membranes. The thermodynamic parameters, structural details, and supramolecular forces are listed to understand the interactions which would help circumvent potential risks and provide guidance for safe use in the future. At the end of this review, future prospective and emerging challenges in this research field are discussed.


Screening methods for high-grade dysplasia in patients with anal condyloma.
Human papilloma virus (HPV) is one of the most common sexually transmitted diseases in the United States. HPV infection can cause anal condylomas and is a risk factor for dysplasia. High-grade dysplasia may progress to squamous cell carcinoma. Currently, biopsy and histological examination are required to grade dysplasia. The purpose of this study is to determine whether anal cytology, morphological characteristics, and/or the presence of high-risk oncogenic HPV-types are effective noninvasive methods to detect high-risk anal condylomas. From November 2003 to June 2004, all patients with anal condyloma were prospectively evaluated for anal cytology, high-risk oncogenic HPV-types, and tissue biopsies. The Bethesda classification system was used to classify cytologic findings and histological examination, which were grouped as high-risk (HRL) and low-risk (LRL) lesions. Histology results served as true disease for all comparisons. Forty-seven patients with anal condyloma were studied; 43 (91.5%) were men, and the mean age was 39 +/- 11 years. Histology showed 19 (40.5%) patients with HRL, and 28 (59.5%) patients with LRL. Cytology correctly identified 8 patients with HRL and 27 patients with LRL (sensitivity 42% and specificity 96%). High-risk oncogenic HPV-types were found in 84.2% of HRL and 39.3% of LRL (P = 0.0029). Combining cytology with oncogenic HPV-testing, the sensitivity of detecting HRL increased to 89%, and specificity decreased to 42%. Anal cytology alone is not accurate for detecting HRL in patients with anal condylomas. Combining oncogenic HPV-testing with cytology is more sensitive in detecting HRL in patients with anal condyloma, and therefore, a more effective screening tool.


Quantitative ultrastructural analysis of a single spinal cord demyelinated lesion predicts total lesion load, axonal loss, and neurological dysfunction in a murine model of multiple sclerosis.
Infection of susceptible mice with Theiler's murine encephalomyelitis virus results in neurological dysfunction from progressive central nervous system demyelination that is pathologically similar to the human disease, multiple sclerosis. We hypothesized that the development of neuropathology proceeds down a final common pathway that can be accurately quantified within a single spinal cord lesion. To test this hypothesis, we conducted quantitative ultrastructural analyses of individual demyelinated spinal cord lesions from chronically infected mice to determine whether pathological variables assessed within a single lesion accurately predicted global assessments of morphological and functional disease course. Within lesions we assessed by electron microscopy the frequencies of normally myelinated, remyelinated, and demyelinated axons, as well as degenerating axons and intra-axonal mitochondria. The frequency of medium and large remyelinated fibers within a single lesion served as a powerful indicator of axonal preservation and correlated with preserved neurological function. The number of degenerating axons and increased intra-axonal mitochondria also correlated strongly with global measures of disease course, such as total lesion load, spinal cord atrophy, and neurological function. This is the first study to demonstrate that functional severity of disease course is evident within a single demyelinated lesion analyzed morphometrically at the ultrastructural level.


Proton transfer in methylmalonyl-CoA epimerase from Propionibacterium shermanii. The reaction of (2R)-methylmalonyl-CoA in tritiated water.
The reaction catalysed by methylmalonyl-CoA epimerase from Propionibacterium shermanii was studied in tritiated water, in the direction with (2R)-methylmalonyl-CoA as substrate, under 'irreversible' conditions. After partial reaction, even when most of the substrate had been converted into product (isolated as propionyl-CoA) essentially no solvent tritium appeared in residual (2R)-methylmalonyl-CoA. The product, however, did contain tritium, and the specific radioactivity of the (2S)-epimer was deduced to be 0.33 times that of the solvent. These results provide further support for the mechanism proposed for the epimerase-catalysed reaction in the accompanying paper [Leadlay & Fuller (1983) Biochem. J. 213, 635-642], in which two enzyme bases act respectively as proton donor and acceptor. The observed low discrimination against solvent tritium entering the product can be accounted for by a mechanism in which the release of product is slow, and the re-protonation step on the enzyme is reversible, without leading to isotopic exchange with the solvent.


Expression and nuclear envelope localization of biologically active fusion glycoprotein gB of herpes simplex virus in mammalian cells using cloned DNA.
Herpes simplex virus (HSV) is known to bud from the inner membrane of the nuclear envelope. The structural gene for the glycoprotein gB, which is essential for virus entry and cell fusion induced by HSV type 1, has been cloned in a transient expression vector containing the adenovirus major late promoter, tripartite leader sequence, and VARNA (a special RNA in adenovirus-infected cells) genes. Synthesis and glycosylation of glycoprotein gB was observed in COS-1 cells transfected with the vector containing the gB gene. Removal of a 3' fragment of the cloned gene resulted in the synthesis and secretion of a truncated gB glycoprotein. Immunofluorescence studies revealed that the expressed glycoprotein was localized in the nuclear envelope as well as in the cell surface. The expressed gB-1 glycoprotein was biologically active and induced fusion of cells to produce polykaryons. These data show that HSV glycoprotein gB expressed from cloned gene can be used as a model to study targeting of proteins into the nuclear envelope as well as cell fusion induced by the virus.


Human embryonic stem cells have a unique epigenetic signature.
Human embryonic stem (hES) cells originate during an embryonic period of active epigenetic remodeling. DNA methylation patterns are likely to be critical for their self-renewal and pluripotence. We compared the DNA methylation status of 1536 CpG sites (from 371 genes) in 14 independently isolated hES cell lines with five other cell types: 24 cancer cell lines, four adult stem cell populations, four lymphoblastoid cell lines, five normal human tissues, and an embryonal carcinoma cell line. We found that the DNA methylation profile clearly distinguished the hES cells from all of the other cell types. A subset of 49 CpG sites from 40 genes contributed most to the differences among cell types. Another set of 25 sites from 23 genes distinguished hES cells from normal differentiated cells and can be used as biomarkers to monitor differentiation. Our results indicate that hES cells have a unique epigenetic signature that may contribute to their developmental potential.


NAG Vibrio cholerae isolated from imported shellfish in Guam.
A survey of imported shellfish available in public markets on the Island of Guam revealed the presence of NAG Vibrio cholerae contamination (10 of 38 sample lots positive) and high coliform counts (21 of 33 sample lots in excess of 2400 per 100 grams). NAG V. cholerae contamination was associated with high coliform counts and origin in fresh or brackish waters rather than saltwater. Further importation of fresh shellfish from other than approved sources was prohibited.


Diagnostic discrepancies between antemortem clinical diagnosis and autopsy findings in pediatric cancer patients.
Prevalence of discrepancies between antemortem clinical diagnoses and postmortem autopsy findings is uncertain in pediatric oncology given improving diagnostic capabilities over time. Primary objective was to describe discrepancies between antemortem and postmortem diagnosis of pediatric cancer deaths. Secondary objective was to compare clinical characteristics of deaths with and without major diagnostic discrepancies. This was a retrospective study that included pediatric cancer patients diagnosed and treated in Ontario and who died from 2003 to 2012. Antemortem clinical diagnoses associated with mortality were determined by reviewing the patient's health records 2 weeks prior to death while the postmortem diagnoses were determined by the autopsy report. Discrepancies among these diagnoses were classified using the Goldman criteria where major discrepancies were directly related to the cause of death in contrast to minor discrepancies. Among the 821 patients who died, 118 (14%) had an autopsy and were included. Of these autopsies, 12 (10%) had a major diagnostic discrepancy between antemortem and postmortem diagnoses. Major discrepancies consisted of opportunistic infections (n = 5), missed cancer diagnosis (n = 3), and organ complications (n = 4). Death in a high acuity setting (12/12, 100% vs. 60/106, 57%; P = 0.003) and treatment-related mortality (12/12, 100% vs. 60/106, 57%; P = 0.003) were significantly associated with major discrepancy. Major diagnostic discrepancy was found in 10% of pediatric oncology autopsies. Missed infections and organ complications were predominant etiologies. Death in a high acuity setting and treatment-related mortality were associated with major diagnostic discrepancies. Autopsies continue to be important for improving diagnostic insight and may improve future clinical care.


H2-dependent mixotrophic growth of N2-fixing Azotobacter vinelandii.
Azotobacter vinelandii can grow with a variety of organic carbon sources and fix N2 without the need for added H2. However, due to an active H2-oxidizing system, H2-dependent mixotrophic growth in an N-free medium was demonstrated when mannose was provided as the carbon source. There was no appreciable growth with either H2 or mannose alone. Both the growth rate and the cell yield were dependent on the concentrations of both substrates, H2 and mannose. Cultures growing mixotrophically with H2 and mannose consumed approximately 4.8 mmol of O2 and produced 4.6 mmol of CO2 per mmol of mannose consumed. In the absence of H2, less CO2 was produced, less O2 was consumed, and cell growth was negligible. The rate of acetylene reduction in mixotrophic cultures was comparable to the rate in cultures grown in N-free sucrose medium. The rate of [14C]mannose uptake of cultures with H2 was greater than with argon, whereas [14C]sucrose uptake was unaffected by the addition of H2; therefore, the role of H2 in mixotrophic metabolism may be to provide energy for mannose uptake. A. vinelandii is not an autotroph, as attempts to grow the organism chemoautotrophically with H2 or to detect ribulose bisphosphate carboxylase activity were unsuccessful.


Atmo-ecometabolomics: a novel atmospheric particle chemical characterization methodology for ecological research.
Aerosol particles play important roles in processes controlling the composition of the atmosphere and function of ecosystems. A better understanding of the composition of aerosol particles is beginning to be recognized as critical for ecological research to further comprehend the link between aerosols and ecosystems. While chemical characterization of aerosols has been practiced in the atmospheric science community, detailed methodology tailored to the needs of ecological research does not exist yet. In this study, we describe an efficient methodology (atmo-ecometabolomics), in step-by-step details, from the sampling to the data analyses, to characterize the chemical composition of aerosol particles, namely atmo-metabolome. This method employs mass spectrometry platforms such as liquid and gas chromatography mass spectrometries (MS) and Fourier transform ion cyclotron resonance MS (FT-ICR-MS). For methodology evaluation, we analyzed aerosol particles collected during two different seasons (spring and summer) in a low-biological-activity ecosystem. Additionally, to further validate our methodology, we analyzed aerosol particles collected in a more biologically active ecosystem during the pollination peaks of three different representative tree species. Our statistical results showed that our sampling and extraction methods are suitable for characterizing the atmo-ecometabolomes in these two distinct ecosystems with any of the analytical platforms. Datasets obtained from each mass spectrometry instrument showed overall significant differences of the atmo-ecometabolomes between spring and summer as well as between the three pollination peak periods. Furthermore, we have identified several metabolites that can be attributed to pollen and other plant-related aerosol particles. We additionally provide a basic guide of the potential use ecometabolomic techniques on different mass spectrometry platforms to accurately analyze the atmo-ecometabolomes for ecological studies. Our method represents an advanced novel approach for future studies in the impact of aerosol particle chemical compositions on ecosystem structure and function and biogeochemistry.


Asymmetric dimerization in a transcription factor superfamily is promoted by allosteric interactions with DNA.
Transcription factors, such as nuclear receptors achieve precise transcriptional regulation by means of a tight and reciprocal communication with DNA, where cooperativity gained by receptor dimerization is added to binding site sequence specificity to expand the range of DNA target gene sequences. To unravel the evolutionary steps in the emergence of DNA selection by steroid receptors (SRs) from monomeric to dimeric palindromic binding sites, we carried out crystallographic, biophysical and phylogenetic studies, focusing on the estrogen-related receptors (ERRs, NR3B) that represent closest relatives of SRs. Our results, showing the structure of the ERR DNA-binding domain bound to a palindromic response element (RE), unveil the molecular mechanisms of ERR dimerization which are imprinted in the protein itself with DNA acting as an allosteric driver by allowing the formation of a novel extended asymmetric dimerization region (KR-box). Phylogenetic analyses suggest that this dimerization asymmetry is an ancestral feature necessary for establishing a strong overall dimerization interface, which was progressively modified in other SRs in the course of evolution.


Fatigue in chronic liver disease: New insights and therapeutic approaches.
The management of fatigue associated with chronic liver disease is a complex and major clinical challenge. Although fatigue can complicate many chronic diseases, it is particularly common in diseases with an inflammatory component. Fatigue can have both peripheral (i.e., neuromuscular) and central (i.e., resulting from changes in neurotransmission within the brain) causes. However, fatigue in chronic liver disease has strong social/contextual components and is often associated with behavioural alterations including depression and anxiety. Given the increasing awareness of patient-reported outcomes as important components of treatment outcomes and clinical research, there is a growing need to better understand and manage this poorly understood yet debilitating symptom. Although several pathophysiological mechanisms for explaining the development of fatigue have been generated, our understanding of fatigue in patients with chronic liver disease remains incomplete. A better understanding of the pathways and neurotransmitter systems involved may provide specific directed therapies. Currently, the management of fatigue in chronic liver disease can involve a combined use of methods to beneficially alter behavioural components and pharmacological interventions, of which several treatments have potential for the improved management of fatigue in chronic liver disease. However, evidence and consensus are lacking on the best approach and the most appropriate biochemical target(s) whilst clinical trials to address this issue have been few and limited by small sample size. In this review, we outline current understanding of the impact of fatigue and related symptoms in chronic liver disease, discuss theories of pathogenesis, and examine current and emerging approaches to its treatment.


[Cardiopathy and stress-inducing factors].
There is wide consensus on the association between work stress and cardiovascular disease, ischaemic heart disease and hypertension in particular, both from the clinical and epidemiological point of view. The aim of this article was to review the most recent data on these topics found in the international literature on occupational health and cardiology. A literature review was performed. The relationship between stress and cardiovascular diseases is mediated by several direct and indirect mechanisms and is related not only to high cognitive and emotional stress but especially to poor coping strategies, which are strongly influenced by lack of control over working conditions and lack of social support. This entails high costs both for the individual and society, not only in terms of workers' health and well-being, but also as regards work ability and performance efficiency, with negative consequences on production and services. Some working activities, where public health is also at stake (such as train, bus and lorry drivers, air pilots and traffic controllers), deserve special attention, due to the well-documented prevalence of job-related cardiovascular disease.


Modification of potassium channel kinetics by amino group reagents.
We have examined the actions of several amino group reagents on delayed rectifier potassium channels in squid giant axons. Three general classes of reagents were used: (1) those that preserved the positive charge of amino groups; (2) those that neutralize the charge; and (3) those that replace the positive with a negative charge. All three types of reagents produced qualitatively similar effects on K channel properties. Trinitrobenzene sulfonic acid (TNBS) neutralizes the peptide terminal amino groups and the epsilon-amino group of lysine groups. TNBS (a) slowed the kinetics of macroscopic ionic currents; (b) increased the size of ionic currents at large positive voltages; (c) shifted the voltage-dependent probability of channel opening to more positive potentials but had no effect on the voltage sensitivity; and (d) altered several properties of K channel gating currents. The actions of TNBS on gating currents suggest the presence of multiple gating current components. These effects are not all coupled, suggesting that several amino groups on the external surface of K channels are important for channel gating. A simple kinetic model that considers the channel to be composed of independent heterologous subunits is consistent with most of the modifications produced by amino group reagents.


Linear parameter-varying model and adaptive filtering technique for detecting neuronal activities: an fNIRS study.
Functional near-infrared spectroscopy (fNIRS) is an emerging non-invasive brain imaging technique that measures brain activities by using near-infrared light of 650-950 nm wavelength. The major advantages of fNIRS are its low cost, portability, and good temporal resolution as a plausible solution to real-time imaging. Recent research has shown the great potential of fNIRS as a tool for brain-computer interfaces. This paper presents the first novel technique for fNIRS-based modelling of brain activities using the linear parameter-varying (LPV) method and adaptive signal processing. The output signal of each channel is assumed to be an output of an LPV system with unknown coefficients that are optimally estimated by the affine projection algorithm. The parameter vector is assumed to be Gaussian. The general linear model (GLM) is very popular and is a commonly used method for the analysis of functional MRI data, but it has certain limitations in the case of optical signals. The proposed model is more efficient in the sense that it allows the user to define more states. Moreover, unlike most previous models, it is online. The present results, showing improvement, were verified by random finger-tapping tasks in extensive experiments. We used 24 states, which can be reduced or increased depending on the cost of computation and requirements. The t-statistics were employed to determine the activation maps and to verify the significance of the results. Comparison of the proposed technique and two existing GLM-based algorithms shows an improvement in the estimation of haemodynamic response. Additionally, the convergence of the proposed algorithm is shown by error reduction in consecutive iterations.


Investigating local policy drivers for alcohol harm prevention: a comparative case study of two local authorities in England.
The considerable challenges associated with implementing national level alcohol policies have encouraged a renewed focus on the prospects for local-level policies in the UK and elsewhere. We adopted a case study approach to identify the major characteristics and drivers of differences in the patterns of local alcohol policies and services in two contrasting local authority (LA) areas in England. Data were collected via thirteen semi-structured interviews with key informants (including public health, licensing and trading standards) and documentary analysis, including harm reduction strategies and statements of licensing policy. A two-stage thematic analysis was used to categorize all relevant statements into seven over-arching themes, by which document sources were then also analysed. Three of the seven over-arching themes (drink environment, treatment services and barriers and facilitators), provided for the most explanatory detail informing the contrasting policy responses of the two LAs: LA1 pursued a risk-informed strategy via a specialist police team working proactively with problem premises and screening systematically to identify riskier drinking. LA2 adopted a more upstream regulatory approach around restrictions on availability with less emphasis on co-ordinated screening and treatment measures. New powers over alcohol policy for LAs in England can produce markedly different policies for reducing alcohol-related harm. These difference are rooted in economic, opportunistic, organisational and personnel factors particular to the LAs themselves and may lead to closely tailored solutions in some policy areas and poorer co-ordination and attention in others.


Oxidative stress and cryoresistance of sturgeon sperm: A review.
Currently, the majority of sturgeons are relict fishes of high economic value yet endangered with extinction. Cryopreservation of sperm has great potential in fish farming and conservation, but the problem of low cryoresistance of sturgeon sperm has not yet been solved. The goal of this work was to review current literature data on the causes of low tolerance of sturgeon sperm to cryodamage. The influence of cryopreservation on the parameters of physiology and metabolism of sturgeon sperm (morphology and fine ultrastructure, mobility and fertilization ability, integrity of the plasma membrane, protein, lipid and metabolite profiles, antioxidant status, DNA damage), as well as on biomarkers of oxidative stress (lipids peroxidation levels and carbonyl derivatives of proteins) is discussed. Since the development of oxidative stress is an important mechanism of sperm cryodamage induction, the review presents the literature on the role of oxygen-derived species in damage of sturgeon reproductive cells caused by cryopreservation. Particular attention is paid to the system of antioxidant protection of sturgeon seminal plasma and spermatozoa, represented by antioxidant enzymes and low molecular weight antioxidants capable of utilizing various reactive forms of oxygen and nitrogen. The review discusses the results of lipidomic and proteomic studies of sturgeon sperm, which made it possible to obtain new data on the lipid composition of cell membranes, to detect proteins involved in the protection of sturgeon spermatozoa from oxidative damage during cryopreservation. This review presents the use of «omics» technology to elucidate the mechanism of cryodamage in sturgeon sperm. Additionally, the review summarizes information on the unique anatomical, morphological, biochemical, and physiological features of sturgeon sperm, which may be associated with low cryoresistance of sturgeon, in order to establish prospects for further research on improving the methods of the conservation of sperm of these threatened species.


Effect of Hepatitis E Virus RNA Universal Blood Donor Screening, Catalonia, Spain, 2017‒2020.
Hepatitis E virus (HEV) is the major cause of acute viral hepatitis in several countries in Europe. HEV is acquired mainly by consumption of contaminated pork but can also be transmitted through blood transfusion. HEV infection is usually self-limited but can become persistent in immunocompromised persons. During the first 30 months of HEV RNA universal screening of blood donations in Catalonia, Spain, we identified 151 HEV RNA-positive donations (1/4,341 blood donations). Most infected donors reported consumption of pates and sausages, and 58% were negative for HEV IgM and IgG. All HEV isolates belonged to genotype 3. All infected donors spontaneously resolved the infection, and no neurologic symptoms and reinfections were observed after 1 year of follow-up. Since the implementation of HEV RNA universal screening, no new cases of transfusion-transmitted HEV infection were reported. Our data indicate HEV screening of blood donations provides safer blood for all recipients, especially for immunosuppressed persons.


microRNA-34a promotes DNA damage and mitotic catastrophe.
Efficient and error-free DNA repair is critical for safeguarding genome integrity, yet it is also linked to radio- and chemoresistance of malignant tumors. miR-34a, a potent tumor suppressor, influences a large set of p53-regulated genes and contributes to p53-mediated apoptosis. However, the effects of miR-34a on the processes of DNA damage and repair are not entirely understood. We explored tet-inducible miR-34a-expressing human p53 wild-type and R273H p53 mutant GBM cell lines, and found that miR-34a influences the broad spectrum of 53BP1-mediated DNA damage response. It escalates both post-irradiation and endogenous DNA damage, abrogates radiation-induced G 2/M arrest and drastically increases the number of irradiated cells undergoing mitotic catastrophe. Furthermore, miR-34a downregulates 53BP1 and inhibits its recruitment to the sites of DNA double-strand breaks. We conclude that whereas miR-34a counteracts DNA repair, it also contributes to the p53-independent elimination of distressed cells, thus preventing the rise of genomic instability in tumor cell populations. These properties of miR-34a can potentially be exploited for DNA damage-effecting therapies of malignancies.


A Comprehensive Review of the (1)H-MRS Metabolite Spectrum in Autism Spectrum Disorder.
Neuroimaging studies of neuropsychiatric behavior biomarkers across spectrum disorders are typically based on diagnosis, thus failing to account for the heterogeneity of multi-dimensional spectrum disorders such as autism (ASD). Control group trait phenotypes are also seldom reported. Proton magnetic resonance spectroscopy ((1)H-MRS) measures the abundance of neurochemicals such as neurotransmitters and metabolites and hence can probe disorder phenotypes at clinical and sub-clinical levels. This detailed review summarizes and critiques the current (1)H-MRS research in ASD. The literature reports reduced N-acetylaspartate (NAA), glutamate and glutamine (Glx), γ-aminobutyric acid (GABA), creatine and choline, and increased glutamate for children with ASD. Adult studies are few and results are inconclusive. Overall, the literature has several limitations arising from differences in (1)H-MRS methodology and sample demographics. We argue that more consistent methods and greater emphasis on phenotype studies will advance understanding of underlying cortical metabolite disturbance in ASD, and the detection, diagnosis, and treatment of ASD and other multi-dimensional psychiatric disorders.


An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion.
Aberrant protein phosphorylation plays important roles in cancer-related cell signaling. With the goal of achieving multiplexed, comprehensive, and fully automated relative quantitation of site-specific phosphorylation, we present a simple label-free strategy combining an automated pH/acid-controlled IMAC procedure and informatics-assisted SEMI (sequence, elution time, mass-to-charge, and internal standard) algorithm. The SEMI strategy effectively increased the number of quantifiable peptides more than 4-fold in replicate experiments (from 262 to 1171, p < 0.05, false discovery rate = 0.46%) by using a fragmental regression algorithm for elution time alignment followed by peptide cross-assignment in all LC-MS/MS runs. In addition, the strategy demonstrated good quantitation accuracy (10-12%) for standard phosphoprotein and variation less than 1.9 fold (within 99% confidence range) in proteome scale and reliable linear quantitation correlation (R(2) = 0.99) with 4000-fold dynamic concentrations, which was attributed to our reproducible experimental procedure and informatics-assisted peptide alignment tool to minimize system variations. In an attempt to explore metastasis-associated phosphoproteomic alterations in lung cancer, this approach was used to delineate differential phosphoproteomic profiles of a lung cancer metastasis model. Without sample fractionation, the SEMI algorithm enabled quantification of 1796 unique phosphopeptides (false discovery rate = 0.56%) corresponding to 854 phosphoproteins from a series of non-small cell lung cancer lines with varying degrees of in vivo invasiveness. Nearly 40% of the phosphopeptides showed >2-fold change in highly invasive cells; validation of phosphoprotein subsets by Western blotting not only demonstrated the consistency of data obtained by our SEMI strategy but also revealed that such dramatic changes in the phosphoproteome result mostly from translational or post-translational regulation. Mapping of these differentially expressed phosphoproteins in multiple cellular pathways related to cancer invasion and metastasis suggests that the site and degree of phosphorylation might have distinct patterns or functions in the complex process of cancer progression.


[The chemotherapeutic efficacy of ciprofloxacin and lomefloxacin in the inhalation method of infecting white mice with tularemia].
Peculiarities of the protective effect of ciprofloxacin and lomefloxacin were studied and the optimal regimens of their use were determined in multifactor experiments on albino mice infected with finally dispersed aerosol of the virulent strain of the European subspecies of Francisella tularensis. As for protective effect, the fluoroquinolones provided high percentage of the animal survival. The optimal course of the treatment was at least 7 days. The interval of 0 to 48 hours between the infection and the start of the treatment had no statistically significant effect on chemotherapeutic efficacy of fluoroquinolones.


TobEA: an atlas of tobacco gene expression from seed to senescence.
Transcriptomics has resulted in the development of large data sets and tools for the progression of functional genomics and systems biology in many model organisms. Currently there is no commercially available microarray to allow such expression studies in Nicotiana tabacum (tobacco). A custom designed Affymetrix tobacco expression microarray was generated from a set of over 40k unigenes and used to measure gene expression in 19 different tobacco samples to produce the Tobacco Expression Atlas (TobEA). TobEA provides a snap shot of the transcriptional activity for thousands of tobacco genes in different tissues throughout the lifecycle of the plant and enables the identification of the biological processes occurring in these different tissues. 772 of 2513 transcription factors previously identified in tobacco were mapped to the array, with 87% of them being expressed in at least one tissue in the atlas. Putative transcriptional networks were identified based on the co-expression of these transcription factors. Several interactions in a floral identity transcription factor network were consistent with previous results from other plant species. To broaden access and maximise the benefit of TobEA a set of tools were developed to provide researchers with expression information on their genes of interest via the Solanaceae Genomics Network (SGN) web site. The array has also been made available for public use via the Nottingham Arabidopsis Stock Centre microarray service. The generation of a tobacco expression microarray is an important development for research in this model plant. The data provided by TobEA represents a valuable resource for plant functional genomics and systems biology research and can be used to identify gene targets for both fundamental and applied scientific applications in tobacco.


Impact of obesity, structural severity and their combination on the efficacy of viscosupplementation in patients with knee osteoarthritis.
Obesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough to formally refute VS in such patients in whom surgery is sometimes contraindicated? To compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined. Post-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.- 2), OARSI radiological grade (1-2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons (obese versus non-obese, OARSI 1-2 versus 3, and both combined) in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test. One-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups (all p < 0.01). At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients (4.9 ± 4.1 versus 7.1 ± 4.9; p = 0.008) and in patients OARSI 1-2 versus 3 (4.8 ± 4.3 versus 6.4 ± 4.5; p = 0.009). However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score. These results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS.


Morbidity of early spine surgery in the multiply injured patient.
The optimal timing of surgery for multiply injured patients with operative spinal injuries remains unknown. The purported benefits of early intervention must be weighed against the morbidity of surgery in the early post-injury period. The performance of spine surgery in the Afghanistan theater permits analysis of the morbidity of early surgery on military casualties. The objective is to compare surgical morbidity of early spinal surgery in multiply injured patients versus stable patients. Patients were retrospectively categorized as stable or borderline unstable depending on the presence of at least one of the following: ISS >40, ISS >20 and chest injury, exploratory laparotomy or thoracotomy, lactate >2.5 mEq/L, platelet <110,000/mm(3), or >10 U PRBCs transfused pre-operatively. Surgical morbidity, complications, and neurologic improvement between the two groups were compared retrospectively. 30 casualties underwent 31 spine surgeries during a 12-month period. 16 of 30 patients met criteria indicating a borderline unstable patient. Although there were no significant differences in the procedures performed for stable and borderline unstable patients as measured by the Surgical Invasiveness Index (7.5 vs. 6.9, p = 0.8), borderline unstable patients had significantly higher operative time (4.3 vs. 3.0 h, p = 0.01), blood loss (1,372 vs. 366 mL, p = 0.001), PRBCs transfused intra-op (3.88 vs. 0.14 U, p < 0.001), and total PRBCs transfused in theater (10.18 vs. 0.31 U, p < 0.001). The results indicate that published criteria defining a borderline unstable patient may have a role in predicting increased morbidity of early spine surgery. The perceived benefits of early intervention should be weighed against the greater risks of performing extensive spinal surgeries on multiply injured patients in the early post-injury period, especially in the setting of combat trauma.


Effect of Cordyceps sinensis on the proliferation and differentiation of human leukemic U937 cells.
Cordyceps sinensis is a herb medicine with antitumor activity capable of suppressing the growth of mouse Sarcoma 180 in vivo. In the present study, we have isolated polysaccharide fraction of Cordyceps sinensis (PSCS) and investigated its effect on the proliferation and differentiation of human leukemic U937 cells using an in vitro culture system. Our results showed that the conditioned medium from PSCS (10 microg/ml)-stimulated blood mononuclear cells (PSCS-MNC-CM) had an activity that could significantly inhibit the proliferation of U937 cells resulting in a growth inhibition rate of 78-83%. Furthermore, PSCS-MNC-CM treatment induced about 50% of the cells differentiating into mature monocytes/macrophages expressing nonspecific esterase (NSE) activity and the surface antigens of CD11b, CD14, and CD 68. Yet, the differentiated U937 cells also had functions of phagocytosis and superoxide production. However, PSCS alone or normal MNC-CM had no such effects. The levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 were very low in normal MNC-CM, and they were greatly increased in MNC-CM prepared with PSCS stimulation. Antibody neutralization studies further revealed that the tumoricidal and differentiating effects of PSCS-MNC-CM were mainly derived from the elevated cytokines, especially IFN-gamma and TNF-alpha. These two cytokines acted synergistically on inhibiting cell growth and inducing differentiation of the target U937 cells.


Copper(II) chemistry of the functionalized macrocycle cyclam tetrapropionic acid.
The Cu(II) complex of H(4)TETP (H(4)TETP = 1,4,8,11-tetraazatetradecane-1,4,8,11-tetrapropionic acid) is five-coordinate with a distorted square-pyramidal structure (τ = 0.45; i.e. the geometry is nearly half-way between square-pyramidal and trigonal-bipyramidal) and a relatively long Cu-N and a short Cu-O bond; the comparison between powder and solution electronic spectroscopy, the frozen solution EPR spectrum and ligand-field-based calculations (angular overlap model, AOM) indicate that the solution and solid state structures are very similar, i.e. the complex has a relatively low "in-plane" and a significant axial ligand field with a d(x(2)-y(2)) ground state. The ligand-enforced structure is therefore shown to lead to a partially quenched Jahn-Teller distortion and to a relatively low complex stability, lower than with the corresponding acetate-derived ligand H(4)TETA. This is confirmed by potentiometric titration and by the biodistribution with (64)Cu-labeled ligands which show that the uptake in the liver is significantly increased with the H(4)TETP-based system.


One-step synthesis of magnetic fly ash composites for methylene blue removal: batch and column study.
This study focuses on the synthesis of magnetic fly ash composites and its application for the removal of methylene blue (MB) from wastewater. By-product of oil power plants, oil fly ash, was treated with magnetic nanoparticles after chemical surface modification and dubbed modified fly ash (MFA). MFA was characterized by X-ray fluorescence, diffractogram analysis, scanning electron microscopy, energy-dispersive X-ray (EDX), and Fourier transform infrared (FT-IR) and N2 physisorption. MB (methylene blue) was removed from an aqueous solution using the response surface modelling (RSM) technique, which was used for optimization reasons. All four independent factors were investigated to see how they affected the removal process: adsorbent dosage; contact time; pH; and beginning dye concentration. The rate of MB removal was strongly influenced by the pH of the solution. The Langmuir and Freundlich models were used to examine equilibrium data A for MB adsorption onto the MFA in linear and nonlinear forms. Langmuir gave a better fit. The adsorption kinetics shown by increased kinetic statistics were better characterized by a pseudo-second-order MFA model. As far as thermodynamic characteristics go, adsorption is endothermic and occurs spontaneously. It has been proven that MFA may be used as an adsorbent to remove MB dye with high efficiency, and the quadratic model has been proved to be statistically significant.


Appearance and evolution of anti-Da (B cell-specific) antibodies after planned immunizations.
Appearance and evolution of anti-Da antibodies has been followed in eight volunteers immunized by whole blood transfusions or leukocyte intradermal injections form a single donor incompatible for HLA--A,--B,--C and--D specificities. Several unabsorbed bleedings from each recipient were studied against the specific immunizer with three different complement-dependent lymphocytotoxicity (CdL) techniques: (1) standard NIH CdL on total peripheral blood lymphocytes (PBL); (2) VII Workshop standard CdL technique on B cell-enriched suspensions; (3) beta2 microglobulin blanketing test ("bb" test) on B cells. Results obtained with the "bb" test were confirmed with platelet-absorbed sera. The "bb" and the absorbed sera allow discrimination between anti-Da and anti-HLA--A,--B,--C antibodies. Stage of appearance and evolution are rather similar for an anti-HLA--A,--B,--C and anti-Da. An early appearance of antibodies positive only against B cells is due to weak anti-HLA--A,--B antibodies which react better with B cells than with total PBL. Immunogenicity of Da antigens seems to be of the same order as HLA--A, and--B. In fact, Da reactivity was present in all eight recipients studied. These reactivities always segregated in familes with these HLA haplotypes. On a small panel of unrelated D-typed donors, three sera showed a significant positive association with D alleles.


Effect of vaccination route and composition of DNA vaccine on the induction of protective immunity against pseudorabies infection in pigs.
Vaccination with naked DNA may be an alternative to conventional vaccines because it combines the efficacy of attenuated vaccines with the biological safety of inactivated vaccines. We recently showed that the vaccination with naked DNA coding for the immunorelevant glycoprotein D (gD) of pseudorabies virus (PRV) induced both antibody and cell-mediated immunity in pigs and provided protection against challenge infection. To determine whether the efficacy of the naked DNA vaccination against PRV could be improved, we compared three sets of variables. First, the efficacy of the naked DNA vaccine coding only for the immunorelevant gD was compared with a cocktail vaccine containing additional plasmids coding for two other immunorelevant glycoproteins, gB and gC. Second, the intramuscular route of vaccination was compared with the intradermal route. Third, the commonly used needle method of inoculation was compared with the needleless Pigjet injector method. Five groups of five pigs were vaccinated three times at 4-weeks intervals and challenged with the virulent NIA-3 strain of PRV 6 weeks after the last vaccination. Results showed that although the cocktail vaccine induced stronger cell-mediated immune responses than the vaccine containing only gD plasmid, both vaccines protected pigs equally well against challenge infection. Intradermal inoculation with a needle induced significantly stronger antibody and cell-mediated immune responses and better protection against challenge infection than intramuscular inoculation. Our data show that the route of administering DNA vaccines in pigs is important for an optimal induction of protective immunity.


Differential patency and limb salvage for polytetrafluoroethylene and autogenous saphenous vein in severe lower extremity ischemia.
Polytetrafluoroethylene (PTFE) was compared to autogenous saphenous vein (ASV) in 133 femoropopliteal and femorotibial or peroneal bypass procedures performed in limb salvage during a 4-year period. PTFE was used as an alternative prosthesis in the absence of a suitable ASV. Sixty-nine femoropopliteal bypasses (FPBPs) were studied--36 with ASV and 33 with PTFE. Sixty-four femorotibial or peroneal bypasses were categorized as femoral distal bypasses (FDBPs)--34 with ASV and 30 with PTFE. With a 3-year clinical follow-up, cumulative function rate (CFR)--patency including thrombectomy--for FPBP with ASV was 65% as compared to 53% for PTFE (P greater than 0.05), whereas the limb salvage rate (LSR) was 75% with ASV and 56% for PTFE (P greater than 0.05). However for FDBP, the GFR was 55% for ASV and 7% for PTFE, whereas the LSR was 55% with ASV and 26% for PTFE. The cumulative patency rate (CPR)--initial thrombosis of a prosthesis as an endpoint--was not significantly (P greater than 0.05) different from CFR, suggesting that thrombectomy with or without distal anastamotic revision does not contribute to patency of the PTFE prosthesis in these limb salvage cases. PTFE was a suitable alternative to ASV for FPBP; however, PTFE is recommended for FDBP in selected cases only.


Is there an optimal "door to cath time" in the treatment of acute pulmonary embolism with catheter-directed thrombolysis?
Ultrasound assisted catheter-directed thrombolysis (UACT) is a relatively novel approach to treating acute pulmonary embolism (PE). It is an alternative to systemic thrombolysis with good success rates and low reported in-hospital mortality, and low rates of procedure-related major and minor bleeding. Since UACT received FDA approval for the treatment of PE in 2014, there is paucity of data regarding the optimal timing of initiation of the procedure after the initial diagnosis is made. We reviewed the available literature regarding UACT for acute PE and found six studies that included time to procedure. Based on our review, patients may benefit from early (<24-48 h after presentation) rather than delayed (>48 h) initiation. Early initiation of therapy has shown to improve pulmonary arterial pressures, right ventricular (RV) to left ventricular (LV) ratios, with low rates of bleeding and low post procedural and in hospital mortality. However, further studies are required to confirm these findings and establish the appropriate timeline for initiation of UACT.


2-hydroxyethyl methacrylate composite - polypropylene mesh for preventing peritoneal adhesions in female dogs.
To evaluate whether the lining facing the visceral side of polypropylene mesh made with 2-hydroxyethyl methacrylate (p(HEMA)) hydrogel could avoid peritoneal adhesion in female dogs. Eight animals (group PP) had a polypropylene mesh implanted to correct a defect in the rectal abdominal muscle, whereas in the other group (group PH) the polypropylene mesh was coated with p(HEMA) composite on the surface facing the peritoneal area. Adhesions were observed on the mesh in 62.5% of the PP group. In the PH group adhesions were present only on the suture lines. p(HEMA) hydrogel was well tolerated and effective in avoiding visceral and omental adhesions on the surface of the polypropylene mesh.


Munchausen syndrome by proxy abuse perpetrated by men.
Fifteen families are described in which one or more child incurred factitious illness abuse as a result of the father's false story and actions. The degree of direct physical harm, and the chance of death, was high in those families in which the father had Munchausen syndrome or marked somatising disorder. Eleven children died and another six survived repetitive smothering or poisoning. Although the extent of the risk to children living with a parent who has marked somatising disorder is unsure, there must be vigilance on behalf of those children.


Prevalence of non-communicable diseases and its risk factors among Ijegun-Isheri Osun residents in Lagos State, Nigeria: a community based cross-sectional study.
The rapid epidemiologic transition of diseases has adverse implications for low-and middle-income countries (LMICs) like Nigeria due to their limited healthcare, weaker health systems and the westernization of lifestyle. There is a need to evaluate the enormity or otherwise of non-communicable diseases (NCDs) burden in such low resource settings. We performed this survey to determine the prevalence of NCDs and its risk factors among the Ijegun- Isheri Osun community residents of Lagos, Nigeria. A community-based cross-sectional survey was performed on 215 respondents recruited consecutively during a population preventive health campaign. Prevalence of three NCDs (hypertension, diabetes and dyslipidaemia) were calculated. Associations between each of these NCDs and selected risk factors were determined using chi square test. Multivariable logistic regression was used to estimate the risk factors of each of the three NCDs. The prevalence of hypertension was 35.3% (95% CI 29.0-42.1), diabetes 4.6% (95% CI 2.2-8.4) and dyslipidaemia 47.1% (95% CI 41.1-54.8). Among the NCD risk factors, the prevalence of smoking was 41.3% (95% CI 34.2-48.6), alcohol consumption 72.5% (95% CI 65.5-78.7), and physical activity 52.9 (95% CI 45.5-60.2). The independent significant predictors of hypertension were age ≥ 60 years (aOR 4.56; 95% CI: 1.72-12.09) and dyslipidaemia (aOR 5.01; 95% CI: 2.26-11.13). Age ≥ 60 years (aOR 8.83; 95% CI: 1.88-41.55) was an independent predictor of diabetes. Age ≥ 60 years (aOR 29.32; 95% CI: 4.78-179.84), being employed (aOR 11.12; 95% CI: 3.10-39.92), smoking (aOR 2.34; 95% CI: 1.03-5.33) and physical activity (aOR 0.34; 95% CI: 0.15-0.76) were independent predictors of having dyslipidaemia. The prevalence of hypertension, diabetes and dyslipidaemia and their associated risk factors are high among the respondents of Ijegun-Isheri Osun community of Lagos state, Nigeria. This highlights the need for further implementation research and policy directions to tackle NCD burden in urban communities in Nigeria. These strategies must be community specific, prioritizing the various risk factors and addressing them accordingly.


Central effects of insulin detemir on feeding, body weight, and metabolism in rats.
Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain-sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the central nervous system. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE), and respiratory quotient (RQ). Also, in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE, and RQ when microinjected directly into the paraventricular nucleus (PVN). The anabolic peptide ghrelin served as a positive control in acute testing. 3V administration of both DET (0.5-2.0 mU) and regular insulin (2.0-8.0 mU) significantly reduced feeding and body weight over 48 and 120 h, respectively, with DET yielding greater inhibitory effects. DET also stimulated greater elevations of EE and reductions of RQ over 72 and 48 h postinjection, respectively. In acute (4 h) testing, microinjections of DET (0.5 mU) into the PVN reduced feeding, increased EE, and reduced RQ, while ghrelin (100 pmol) had the opposite effects. When administered sequentially into the PVN, DET (0.25 and 0.5 mU) reversed ghrelin-induced feeding, EE, and RQ effects. These data support the notion that the weight-sparing effect of DET is at least in part based on its central catabolic action and that enhanced EE and reduced RQ may participate in this effect.


Effects of PTH, ADH, and cyclic AMP on distal tubular Ca and Na reabsorption.
Tubular microperfusion experiments were performed in rats to examine the effects of thyroparathyroidectomy (TPTX), parathyroid hormone (PTH), antidiuretic hormone (ADH), and cyclic AMP (cAMP) on distal tubular Ca, Na, and water reabsorption. TPTX caused a significant decrease in the Ca reabsorptive rate as compared to intact animals. PTH (5 U/kg; 2 U x kg-1 x h-1) replacement in TPTX animals restored Ca transport to control levels. Application of either cAMP (10(-3) M) or 8-(p-chlorophenylthio)-cyclic 3',5'-adenosine monophosphate (10(-5) M) to the surface of the kidney caused a stimulation of Ca reabsorption similar to that produced by PTH. Neither TPTX nor PTH changed Na or water reabsorption significantly, whereas the cyclic nucleotides increased both of these parameters. These later actions of cAMP duplicated effects of ADH observed in these distal tubules.


Effect of methamidophos on soil fungi community in microcosms by plate count, DGGE and clone library analysis.
Methamidophos was widely used a pesticide in northern China. The potential influences of methamidophos on soil fungal community in black soil were assessed by plate count, 28S rDNA-PCR-DGGE, and clone library analysis. Three methamidophos levels (50, 150, and 250 mg/kg) were tested in soil microcosms. Results from plate count during a 60-d microcosm experiment showed that high concentrations of methamidophos (250 mg/kg) could significantly stimulate fungal populations. DGGE (denaturing gradient gel electrophoresis) fingerprinting patterns showed a significant difference between the responses of culturable and total fungi communities under the stress of methamidophos. Shannon diversity indices calculated from DGGE profiles indicated that culturable fungi in all microcosms with methamidophos treatment increased after 1 week of incubation. However, the diversity indices of total fungi decreased in the first week, as compared to the stimulation of culturable fungi. At the 8th week, however, all the microcosms treated by methamidophos were similar to the control microcosms in community structure as suggested by the Shannon diversity indices for both culturable and total fungi. In contrast, after 1 week the fungal structure of culturable and unculturable both were disturbed to different extent under the stresses of methamidophos by clustering analysis. Clone sequencing analysis indicated the stimulation of pathogenic and unculturable fungal populations by methamidophos treatment, suggetsing potential risks of plant disease outbreak.


[Clinical characteristics of influenza acute respiratory distress syndrome in 2017 to 2018].
Objective: To describe the clinical characteristics of acute respiratory distress syndrome (ARDS) caused by severe influenza virus in our hospital. Method: From November 2017 to February 2018, 48 patients were diagnosed with ARDS caused by influenza virus pneumonia. There characteristics, treatment, and outcomes were summarized and analyzed. According to the prognosis, the patients were divided into a survival group and a death group for comparative analysis. The multivariable logistic regression analysis was used for risk factors of hospital mortality. Result: Thirty-one patients were confirmed to have influenza A virus infection, 3 influenza B virus, 2 mixed infection, while 12 patients were diagnosed by clinical criteria. Eighteen patients died, with a mortality of 38%. Twenty-six patients (54%) were co-infected by other pathogenic microorganisms, including 17 cases of invasive aspergillus infection. Sixteen patients (33%) acquired nosocomial infection that significantly correlated with the hospital mortality, P=0.003. Multivariable logistic regression analysis showed that higher age (OR=1.086, 95% CI: 1.016-1.016), P=0.015), longer duration of flu-like symptoms to RICU time (OR=1.196, 95% CI: 1.031-1.031, P=0.018) and lower PaO(2)/FiO(2) (OR=0.973, 95% CI: 0.951-0.951, P=0.017) were independent risk factors for hospital mortality. Conclusion: In the flu season of 2017-2018, the patients of ARDS caused by severe influenza pneumonia were mainly influenza A virus, with a mortality of 38%. Co-infection was very common, especially aspergillus infection. Nosocomial infection was common and significantly correlated with high mortality. Lower PaO(2)/FiO(2), higher age and the longer duration from influenza-like symptoms to RICU was independent risk factors for high hospital mortality.


Genetic characterisation of cercarial stages of Choanocotyle Jue Sue and Platt, 1998 (Digenea: Choanocotylidae) in a native Australian freshwater snail, Isidorella hainesii (Tryon).
Isidorella hainesii (Tryon, 1866) is a native freshwater snail, belonging to the family Planorbidae, commonly found on aquatic vegetation in south eastern parts of Australia. In the present study, we report natural infection with a species of Choanocotyle Jue Sue and Platt, 1998 (Digenea: Choanocotylidae) parasite in inland Australia for the first time, followed by characterisation of the parasite using both morphological and molecular approaches. Snails (n = 150) were collected from recently drained, natural ponds at a local fish farm located in the Riverina region, New South Wales, Australia. Parasites were subjected to preliminary morphological examination followed by DNA extraction to obtain their ITS-2, 18S and 28S sequences. Based on their sequence data and phylogenetic analyses they were identified as Choanocotyle hobbsi Platt and Tkach, 2003, which has only previously been described from Chelodina oblonga Gray, 1841 (snake-necked turtle) in Western Australia. Previous researchers suggested that in Australia, C. oblonga and its parasite fauna are separated from their eastern counterparts due to formation of impenetrable waterless desert in the country during the late Cretaceous. Our study extends the distribution of Choanocotyle hobbsi from Western Australia to the Murray Darling Basin in New South Wales, however, the definitive host remains unknown in New South Wales.


Development and Psychometric Properties of the Sleep Parenting Scale for Infants.
Although infants' sleep behaviors are shaped by their interactions with parents at bedtime, few tools exist to capture parents' sleep parenting practices. This study developed a Sleep Parenting Scale for Infants (SPS-I) and aimed to (1) explore and validate its factorial structure, (2) examine its measurement invariance across mothers and fathers, and (3) investigate its reliability and concurrent and convergent validity. SPS-I was developed via a combination of items modified from existing scales and the development of novel items. Participants included 188 mothers and 152 mother-father dyads resulting in 340 mothers and 152 fathers; about half were non-Hispanic white. Mothers and fathers completed a 14-item SPS-I for their 12-month-old infant. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to explore and validate SPS-I's underlying structure. Multigroup CFA was used to examine measurement invariance across mothers and fathers. Reliability was examined using Cronbach's alpha. Concurrent validity was assessed using linear regressions examining associations between SPS-I factors and parent-reported infants nighttime sleep duration. Convergent validity was assessed using paired-sample t-tests to test whether the SPS-I subscale scores were similar between mothers and fathers in the same household. EFA and CFA confirmed a 3-factor, 12-item model: sleep routines, sleep autonomy, and screen media in the sleep environment. SPS-I was invariant across mothers and fathers and was reliable. Concurrent and convergent validity were established. SPS-I has good psychometric properties, supporting its use for characterizing sleep routines, sleep autonomy, and screen media in the sleep environment by mothers and fathers.Supplemental data for this article is available online at https://doi.org/10.1080/08964289.2021.2002799 .


Influence of Diabetes complications and limitations on health-related quality of life: a study in a southeastern Brazilian city.
The aim of this study was to measure how diabetes, its complications, and limitations are associated to the domains of health-related quality of life (HRQoL). A population-based cross-sectional study was conducted with 2178 individuals from the 2014/2015 City of Campinas Health Survey. The SF-36 was used to measure HRQoL. Mean scores were calculated. Crude and adjusted beta coefficients were estimated using multiple linear regression. Diabetes was associated with a significant reduction in the scores of five SF-36 domains. However, no significant reduction of scores was found among diabetics without complications and with no reports of limitations. The reduction in HRQoL was more accentuated with the increase in the number of complications. Three domains were affected in diabetics with one complication and all were affected in those with two or more complications, especially the role physical, role emotional, and physical functioning. Five domains were affected among diabetics who reported some degree of limitation and all were affected in those who reported high degree of limitation. Patients who reported limitation even in the absence of complications had reductions of the scores especially in the role emotional and social functioning. The results reveal that the association between diabetes and HRQoL only prevail in the occurrence of complications and limitations imposed by the disease, indicating the necessity to avoid or delay the emergence of chronic complications with adequate control methods and paying attention to the perception of limitation reported by the patient.


Visual wavelength discrimination by the loggerhead turtle, Caretta caretta.
Marine turtles are visual animals, yet we know remarkably little about how they use this sensory capacity. In this study, our purpose was to determine whether loggerhead turtles could discriminate between objects on the basis of color. We used light-adapted hatchlings to determine the minimum intensity of blue (450 nm), green (500 nm), and yellow (580 nm) visual stimuli that evoked a positive phototaxis (the phototaxis "threshold" [pt]). Juvenile turtles were later trained to associate each color (presented at 1 log unit above that color's pt) with food, then to discriminate between two colors (the original rewarded stimulus plus one of the other colors, not rewarded) when both were presented at 1 log unit above their pt. In the crucial test, turtles were trained to choose between the rewarded and unrewarded color when the colors varied in intensity. All turtles learned that task, demonstrating color discrimination. An association between blue and food was acquired in fewer trials than between yellow and food, perhaps because some prey of juvenile loggerheads in oceanic surface waters (jellyfishes, polyps, and pelagic gastropods) are blue or violet in color.


The FUT2 Variant c.461G>A (p.Trp154*) Is Associated With Differentially Expressed Genes and Nasopharyngeal Microbiota Shifts in Patients With Otitis Media.
Otitis media (OM) is a leading cause of childhood hearing loss. Variants in FUT2, which encodes alpha-(1,2)-fucosyltransferase, were identified to increase susceptibility to OM, potentially through shifts in the middle ear (ME) or nasopharyngeal (NP) microbiotas as mediated by transcriptional changes. Greater knowledge of differences in relative abundance of otopathogens in carriers of pathogenic variants can help determine risk for OM in patients. In order to determine the downstream effects of FUT2 variation, we examined gene expression in relation to carriage of a common pathogenic FUT2 c.461G>A (p.Trp154*) variant using RNA-sequence data from saliva samples from 28 patients with OM. Differential gene expression was also examined in bulk mRNA and single-cell RNA-sequence data from wildtype mouse ME mucosa after inoculation with non-typeable Haemophilus influenzae (NTHi). In addition, microbiotas were profiled from ME and NP samples of 65 OM patients using 16S rRNA gene sequencing. In human carriers of the FUT2 variant, FN1, KMT2D, MUC16 and NBPF20 were downregulated while MTAP was upregulated. Post-infectious expression in the mouse ME recapitulated these transcriptional differences, with the exception of Fn1 upregulation after NTHi-inoculation. In the NP, Candidate Division TM7 was associated with wildtype genotype (FDR-adj-p=0.009). Overall, the FUT2 c.461G>A variant was associated with transcriptional changes in processes related to response to infection and with increased load of potential otopathogens in the ME and decreased commensals in the NP. These findings provide increased understanding of how FUT2 variants influence gene transcription and the mucosal microbiota, and thus contribute to the pathology of OM.


Sphingolipids and brain resident macrophages in neuroinflammation: an emerging aspect of nervous system pathology.
Sphingolipid metabolism is deeply regulated along the differentiation and development of the central nervous system (CNS), and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system. Microglia are resident macrophages of the CNS involved in general maintenance of neural environment. Modulations in microglia phenotypes may contribute to pathogenic forms of inflammation. Since defects in macrophage/microglia activity contribute to neurodegenerative diseases, it will be essential to systematically identify the components of the microglial cell response that contribute to disease progression. In such complex processes, the sphingolipid systems have recently emerged to play important roles, thus appearing as a key new player in CNS disorders. This review provides a rationale for harnessing the sphingolipid metabolic pathway as a potential target against neuroinflammation.


The N. gonorrhoeae type IV pilus stimulates mechanosensitive pathways and cytoprotection through a pilT-dependent mechanism.
The Neisseria gonorrhoeae type IV pilus is a retractile appendage that can generate forces near 100 pN. We tested the hypothesis that type IV pilus retraction influences epithelial cell gene expression by exerting tension on the host membrane. Wild-type and retraction-defective bacteria altered the expression of an identical set of epithelial cell genes during attachment. Interestingly, pilus retraction, per se, did not regulate novel gene expression but, rather, enhanced the expression of a subset of the infection-regulated genes. This is accomplished through mitogen-activated protein kinase activation and at least one other undefined stress-activated pathway. These results can be reproduced by applying artificial force on the epithelial membrane, using a magnet and magnetic beads. Importantly, this retraction-mediated signaling increases the ability of the cell to withstand apoptotic signals triggered by infection. We conclude that pilus retraction stimulates mechanosensitive pathways that enhance the expression of stress-responsive genes and activate cytoprotective signaling. A model for the role of pilus retraction in influencing host cell survival is presented.


Lamina Fenestration Technique for Treatment of Thoracic Ossified Ligamentum Flavum: 2-Year Follow-Up Result.
Background The incidence of thoracic ossification of ligamentum flavum (OLF) is increasing, and the available surgical techniques were invasive. Study Aims To evaluate the surgical outcome and prognostic factors in relation to clinicoradiologic variables with a novel minimally invasive lamina fenestration technique in patients with thoracic OLF. Patients and Methods Between July 2005 and November 2010, 27 levels with 50 lesions in 17 patients were treated with the lamina fenestration technique for the decompression of thoracic OLF. This technique creates a keyhole in the lamina, preserving lower lamina bone, facet joint, and ligamentum flavum. Patient outcome was analyzed using the Japanese Orthopaedic Association (JOA) score and progression of kyphosis on simple X-ray. Results All patients were successfully treated with the laminar fenestration technique. There was one dural tear but no neural complication or injury. Mean length of follow-up was 49 months. Mean JOA score improved from 4.88 to 7 (p = 0.000). Six patients had an excellent surgical outcome; 10 had a good surgical outcome according to JOA scoring. Conclusion The lamina fenestration technique for the treatment of thoracic OLF had a successful outcome with few complications. This technique can be a minimally invasive surgical option for the treatment of thoracic OLF.