Microscopic, immunocytochemical, and ultrastructural properties of peri-implant mucosa in humans.
Microscopic and immunocytochemical studies have demonstrated both similarities and differences between the gingival mucosa and the peri-implant mucosa restored around dental implants. This study was performed on 10 samples of peri-implant mucosa from 10 patients who had undergone implant treatment 16 to 18 months before. Microscopic, ultrastructural, and immunocytochemical investigations were performed to characterize the epithelial and connective layers of the peri-implant mucosa. All specimens showed the morphologic characteristics of well restored tissues. The immunocytochemical reactions used to detect cytokeratins demonstrated that the restored peri-implant mucosa had a non-keratinized epithelium. The apical part of the inner epithelium was a few cell layers thick, like the corresponding junctional epithelium, but it stained positively with the markers for the cytokeratins expressed by the stratified epithelia. Ultrastructurally the keratinocytes adjacent to the implant displayed nuclei containing a rich cytoplasm with filaments and specialized intercellular junctions right up to the more superficial strata. Immunocytochemical reactions and ultrastructural observations demonstrated the presence of non-keratinocyte cells; i.e., Langerhans cells, melanocytes, and Merkel cells. Several cells were found to be proliferating by immunoreaction with mAb anti-PCNA, while immunoreactions with mAbs to detect von Willebrand factor, CD34, and vascular endothelial growth factor marked the well-developed networks of blood and lymphatic vessels in the connective tissue. S-100 and protein gene product 9.5 positive nerve fibers were marked. Immunocytochemical reactions with mAbs anti-vimentin, anti-laminin were also performed. Our results demonstrated that all the epithelial and connective components of the mucosa are involved in the substantial regrowth of the peri-implant tissue and subsequently in the success of the implant.


CDKL1 promotes tumor proliferation and invasion in colorectal cancer.
CDKL1 is a member of the cell division cycle 2 (CDC2)-related serine threonine protein kinase family and is overexpressed in malignant tumors such as melanoma, breast cancer, and gastric cancer. This study aimed to evaluate whether CDKL1 can serve as a potential molecular target for colorectal cancer therapy. Expression of CDKL1 in colorectal cancer tissues and cell lines was measured by immunohistochemistry and Western blot, respectively. To investigate the role of CDKL1 in colorectal cancer, CDKL1-small hairpin RNA-expressing lentivirus was constructed and infected into HCT116 and Caco2 cells. The effects of RNA interference (RNAi)-mediated CDKL1 downregulation on cell proliferation and invasion were assessed by CCK-8, colony formation, transwell, and tumorigenicity assays in nude mice. The effects of CDKL1 downregulation on cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, microarray method and data analysis elucidated the molecular mechanisms underlying the phenomenon. CDKL1 protein was overexpressed in colorectal cancer tissues compared with paired normal tissues. Knockdown of CDKL1 in HCT116 and Caco2 significantly inhibited cell growth, colony formation ability, tumor invasion, and G1-S phase transition of the cell cycle. The knockdown of CDKL1 stimulated the upregulation of p15 and retinoblastoma protein. CDKL1 plays a vital role in tumor proliferation and invasion in colorectal cancer in vitro and in vivo and, thus, may be considered as a valuable target for therapeutic intervention.


cRGD mediated redox and pH dual responsive poly(amidoamine) dendrimer-poly(ethylene glycol) conjugates for efficiently intracellular antitumor drug delivery.
To improve antitumor efficiency of chemotherapy and reduce side effect, according to the physiological characteristics of tumor tissues and tumor intracellular microenvironment, a multifunctional drug delivery system with properties of long circulation, active targeting, redox and pH triggered drug release was established based on the Generation 4 polyamidoamine dendrimer (PAMAM). First, the redox cleavable disulfide bonds (SS) were introduced for linking polyethylene glycol (PEG) with PAMAM to form PAMAM-S-S-PEG (PSSP). Then cRGD peptide was applied to the PEG end of PSSP to construct RGD-PSSP conjugates. Finally, encapsulating the antitumor chemotherapy drug doxorubicin (DOX) into the hydrophobic cavity of RGD-PSSP conjugates constructed the RGD-PSSP/DOX drug delivery system. The in vitro experiments displayed that RGD-PSSP/DOX NPs showed obviously redox and pH dual sensitive drug release profile. MTT and cell uptake observation elucidated cRGD modification could increase the cytotoxicity, and promote the uptake of B16 cells and HUVEC cells both overexpressing integrin ανβ3on cell membrane. Cell uptake mechanism investigation further revealed that RGD-PSSP/DOX interacted with plasma membrane via specific recognition of cRGD peptide with integrin ανβ3, and was subsequently internalized mainly through clathrin- and caveolin-mediated endocytosis. Remarkably, RGD-PSSP/DOX presented superior anticancer activity and lower heart and kidney toxicity in vivo, which could be regarded as a potential candidate for efficient antitumor chemotherapy drug delivery.


Long non-coding RNA FENDRR inhibits cell proliferation and is associated with good prognosis in breast cancer.
FENDRR is a long non-coding RNA (lncRNA) that mediates the modification of the epigenetic landscape of target promoters by binding to polycomb repressive complex 2. However, the role of FENDRR in breast cancer remains unknown. We detected the expression of FENDRR in 52 breast cancer patients' tissues and five breast cancer cell lines. The association between FENDRR expression and clinicopathological features and prognosis of breast cancer patients was also analyzed. Moreover, cell proliferation assays, flow cytometry analysis, wound-healing assays, and transwell migration assays were performed to detect the biological effects of FENDRR in the breast cancer cells. A xenograft model was used to explore the role of FENDRR expression on tumor growth. We found that FENDRR expression was lower in breast cancer cell lines and cancerous tissues than in the adjacent normal tissues. Low expression of FENDRR was associated with a shorter overall survival and a shorter progression-free survival in breast cancer patients (p<0.001, p<0.001, respectively). We found that FENDRR inhibits breast cancer cell proliferation and migration and promotes cell apoptosis, while FENDRR knockdown promotes breast cancer cell proliferation and migration and suppresses cell apoptosis. Finally, we also detected that FENDRR overexpression could inhibit tumor growth in a xenograft model. Our data suggested that FENDRR inhibits breast cancer cell proliferation, promotes cell apoptosis, and is associated with good prognosis in breast cancer. Thus, FENDRR plays an important role in the growth and progression of breast cancer.


Feature Surfaces in Symmetric Tensor Fields Based on Eigenvalue Manifold.
Three-dimensional symmetric tensor fields have a wide range of applications in solid and fluid mechanics. Recent advances in the (topological) analysis of 3D symmetric tensor fields focus on degenerate tensors which form curves. In this paper, we introduce a number of feature surfaces, such as neutral surfaces and traceless surfaces, into tensor field analysis, based on the notion of eigenvalue manifold. Neutral surfaces are the boundary between linear tensors and planar tensors, and the traceless surfaces are the boundary between tensors of positive traces and those of negative traces. Degenerate curves, neutral surfaces, and traceless surfaces together form a partition of the eigenvalue manifold, which provides a more complete tensor field analysis than degenerate curves alone. We also extract and visualize the isosurfaces of tensor modes, tensor isotropy, and tensor magnitude, which we have found useful for domain applications in fluid and solid mechanics. Extracting neutral and traceless surfaces using the Marching Tetrahedra method can cause the loss of geometric and topological details, which can lead to false physical interpretation. To robustly extract neutral surfaces and traceless surfaces, we develop a polynomial description of them which enables us to borrow techniques from algebraic surface extraction, a topic well-researched by the computer-aided design (CAD) community as well as the algebraic geometry community. In addition, we adapt the surface extraction technique, called A-patches, to improve the speed of finding degenerate curves. Finally, we apply our analysis to data from solid and fluid mechanics as well as scalar field analysis.


The effect of choice on memory: The role of theta oscillations.
People value the opportunity to exercise control over the environment or make their own choices. Recent studies have revealed that simply having the opportunity to make choices can facilitate memory performance, suggesting an interaction between reward (due to choice making) and memory systems. However, little is known about the electrophysiological basis of choice-related memory. In the current study, we used scalp electroencephalography combined with a choice encoding task to examine the role of theta oscillations (which have been widely connected to reward and memory processing) in choice-related memory formation. The encoding task had two conditions. In the choice condition, participants were asked to choose between two occluded memoranda by themselves, whereas in the fixed condition, the decision was made by the computer. Behavioral results showed the choice effect, with better performance in the choice condition than the fixed condition on the recognition test given after a 24-h delay. Increases in theta power during an early latency of encoding period predicted successful memory formation in the choice condition, but not in the fixed condition. Furthermore, decreases in theta power during a late latency predicted successful memory formation in both the fixed and the choice conditions. Finally, we observed increased theta power in the choice condition compared to the fixed condition during an early latency of encoding period and decreased theta power in the choice condition compared to the fixed condition during a late latency. Our results suggest that theta oscillations play a significant role in choice-related memory formation.


Syntheses, molecular structures and pH-dependent monomer-dimer equilibria of Dawson alpha2-monotitanium(IV)-substituted polyoxometalates.
The preparation and structural characterization of a novel, solid Brønsted acid based on Dawson alpha2-monotitanium(IV)-substituted polyoxometalates (POMs) are described. The free-acid form of the POM, i.e., 13H+-heteropolyacid with the formula H13[1b].55H2O DH-1 (1b = [(alpha2-P2W17TiO61)(alpha2-P2W17TiO61H)(mu-O)]13-), was prepared by passing an aqueous solution containing a potassium salt precursor, K14[1a].17H2O DK-1 (1a=[(alpha2-P2W17TiO61)2(mu-O)]14-), through a cation-exchange resin column. Compound DK-1 was obtained by a stoichiometric reaction of mono-lacunary Dawson POM [alpha2-P2W17O61]10- with Ti(SO4)2 in an aqueous solution. [Note: the abbreviations D, M, K and H stand for dimer, monomer, potassium salt and free-acid form, respectively.] Compounds DK-1 and DH-1 were characterized by using complete elemental analysis, thermogravimetric (TG) and differential thermal analysis (DTA), FTIR, solution (31P and 183W) NMR spectroscopy, pH-varied 31P NMR spectroscopy, solid-state 31P CPMAS NMR, X-ray crystallography and acidity measurements in an organic solvent with a Hammett indicator for DH-1. The monomeric form, K8[alpha2-P2W17TiO62]. 18H2O MK-1, was derived from DK-1. The molecular structure of 1b was composed of a dimer connected through one Ti-O-Ti bond between two alpha2-mono-Ti(IV)-substituted Dawson POM subunits. BVS (bond valence sum) calculation showed that one oxygen atom (O(60A)) in one of the two Dawson subunits was protonated, therefore the two subunits were unequivalent. On the other hand, the molecular structure of la was a Ti-O-Ti bonding dimer of two equivalent Dawson subunits. The pH-varied 31P NMR spectra of DK-1 and DH-1 in aqueous solutions showed that the monomer at pH 7.0, the dimer at pH 1.0-3.0, and the mono-protonated species of the dimer at pH 0.5 were the predominant species in the solutions. The Hammett acidity constant (H0) of DH-1 in CH3CN (-2.87) was estimated to be almost the same as that of homo-Dawson heteropolyacid H6[P2W18O62].17H2O(-2.77).


[Analysis of Coding Quality of Death Certificates and Autopsy Rates in Chemnitz: 2010-2013].
Postmortem examination as the last service of physicians has been increasingly criticized recently. The aim of this project was to study the influence of place of death, type of postmortem physician, age and sex of the deceased person on the completeness and quality of ICD-10 coding of death certificates issued by physicians in Chemnitz, Germany. We reviewed 15 612 death certificates and 353 autopsy reports of the health office of Chemnitz for the years 2010-2013. We extracted age and sex of the deceased, causes of death as based on the primary postmortem examination and after autopsy if applicable, type of death (natural or unnatural cause of death), and complications as discovered at the second postmortem examination before cremation. In addition, we documented the place of death and type of physician carrying out the postmortem examination. Furthermore, we corrected the inappropriate or missing ICD-10 codes followed by agreement analysis. The analysis was in agreement with the rules of the German Institute of Medical Documentation and Information. The autopsy rate was 2.3%. The underlying condition was not documented in 34.1% of the cases. The agreement between quality-controlled ICD-10 coding of the cause of death and the original ICD-10 coding (three-digit codes) was high (96.5%). High age at death, death not occurring in hospitals, and postmortem examination not carried out in hospitals were associated with a higher probability of ICD-10 miscoding. The observed agreement of 3-digit ICD-10 coded underlying condition after primary postmortem examination and after autopsy was 26.3%. The underlying cause of death contained garbage codes in 24.2%, that is, codes that are inappropriate for cause of death statistics. Physicians have to be sensitized to the need for appropriate documentation of causes of death. Autopsy very frequently resulted in a change of the assessment of the underlying cause of death and therefore remains an important quality control measure for certification on the cause of death. ICD-10 coding of causes of death is not a primary task of physicians and physicians should not be required by law to carry out this task.


Reactivity landscape of pyruvate under simulated hydrothermal vent conditions.
Pyruvate is an important "hub" metabolite that is a precursor for amino acids, sugars, cofactors, and lipids in extant metabolic networks. Pyruvate has been produced under simulated hydrothermal vent conditions from alkyl thiols and carbon monoxide in the presence of transition metal sulfides at 250 °C [Cody GD et al. (2000) Science 289(5483):1337-1340], so it is plausible that pyruvate was formed in hydrothermal systems on the early earth. We report here that pyruvate reacts readily in the presence of transition metal sulfide minerals under simulated hydrothermal vent fluids at more moderate temperatures (25-110 °C) that are more conducive to survival of biogenic molecules. We found that pyruvate partitions among five reaction pathways at rates that depend upon the nature of the mineral present; the concentrations of H2S, H2, and NH4Cl; and the temperature. In most cases, high yields of one or two primary products are found due to preferential acceleration of certain pathways. Reactions observed include reduction of ketones to alcohols and aldol condensation, both reactions that are common in extant metabolic networks. We also observed reductive amination to form alanine and reduction to form propionic acid. Amino acids and fatty acids formed by analogous processes may have been important components of a protometabolic network that allowed the emergence of life.


Entomopathogenic fungi to control bark beetles: a review of ecological recommendations.
There is considerable interest in applying entomopathogenic fungi as a biological control to limit insect populations due to their low environmental and human applicator impacts. However, despite many promising laboratory tests, there are few examples where these fungi were successfully applied to manage bark beetles. Here, we explore how environmental conditions unique to bark beetle habitats may have limited previous entomopathogenic fungus applications, including variable temperatures, ultraviolet light, bark beetle symbiotic microorganisms, tree phytochemicals, and cryptic bark beetle behaviors. Based on the existing literature, we provide a framework for interpreting the pathogenicity of entomopathogenic fungi to bark beetles, with emphasis on both standardizing and improving laboratory approaches to enhance field applications. Our synthesis indicates that most previous laboratory evaluations are conducted under conditions that are not representative of actual bark beetle systems; this may render fungal isolates functionally non-pathogenic in field settings. We recommend that future studies place particular effort into understanding entomopathogen response to the presence of bark beetle symbiotic microorganisms, plant phytochemicals, and potential as a tree endophyte. Additionally, field application methods should aid entomopathogens in overcoming stressful conditions and allow the fungus to infect multiple bark beetle life stages. © 2021 Society of Chemical Industry.


[Treatment of systemic arterial hypertension].
The World Health Organization (WHO) and several other international committees on the study of hypertension define that a patient with blood pressure between 140/90-150/95 mmHg must be treated. In the first stage of hypertension it is possible to modify it with life style changes, but if high blood pressure persists, then drug therapy must be evaluated carefully. Drug therapy management is individualized and based upon age, race, previous history of hypertension, and risks for target systemic organs. At the National Institute of Cardiology "Ignacio Chávez" in Mexico City there is a wide experience with drugs of several groups, and treatment is chosen to give the patient the greatest advantage and quality of life. Nursing requires a clear and precise knowledge of drug therapy in hypertension, as well as the understanding of its physiopathology to support in an effective way each one of the interventions. Through the Nursing process, Nurses direct their actions not only to the correct administration of drugs, but also, based on the patients background, to orient, inform, and educate the patient about disease to achieve a strict drug therapy compliance, in order to reach the main goal of the process, the which is the best quality of life possible.


Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS): study protocol for a randomised controlled trial.
Chronic obstructive pulmonary disease (COPD) is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. We investigate whether long-term therapy with macrolide antibiotics can prevent exacerbations in patients with COPD. Additionally, our study aims to assess the effect of long-term use of macrolide on the development of antimicrobial resistance and on inflammatory parameters related to COPD. We believe this study will provide more data on the effects of macrolide treatment in patients in COPD and will add more knowledge on its working mechanisms. http://www.clinicaltrials.gov NCT00985244.


Polysilicon based flexible temperature sensor for high spatial resolution brain temperature monitoring.
In this paper, we present a flexible temperature sensor with ultra-small polysilicon thermistors for brain temperature monitoring. In vitro sensitivity, resolution, thermal hysteresis and long term stability tests were performed. Temperature coefficient of resistance (TCR) of -0.0031/ °C and resolution of 0.1 °C were obtained for the sensor. Thermal hysteresis for temperature range of 30~45 °C was less than 0.1 °C. With silicon nitride as the passivation layer, the temperature sensor showed a drift within 0.3 °C for 3 days long term stability test in water. In vivo tests showed a clear correlation between the localized brain temperature and electrocorticography (ECoG) signal during spreading depolarization. The developed flexible temperature sensor with small size polysilicon thermistors can be adopted for high resolution brain temperature mapping as well as multimodal monitoring with limited sensing space.


Fossils impact as hard as living taxa in parsimony analyses of morphology.
Systematists disagree whether data from fossils should be included in parsimony analyses. In a handful of well-documented cases, the addition of fossil data radically overturns a hypothesis of relationships based on extant taxa alone. Fossils can break up long branches and preserve character combinations closer in time to deep splitting events. However, fossils usually require more interpretation than extant taxa, introducing greater potential for spurious codings. Moreover, because fossils often have more "missing" codings, they are frequently accused of increasing numbers of MPTs, frustrating resolution and reducing support. Despite the controversy, remarkably little is known about the effects of fossils more generally. Here we provide the first systematic study, investigating empirically the behavior of fossil and extant taxa in 45 published morphological data sets. First-order jackknifing is used to determine the effects that each terminal has on inferred relationships, on the number of MPTs, and on CI' and RI as measures of homoplasy. Bootstrap leaf stabilities provide a proxy for the contribution of individual taxa to the branch support in the rest of the tree. There is no significant difference in the impact of fossil versus extant taxa on relationships, numbers of MPTs, and CI' or RI. However, adding individual fossil taxa is more likely to reduce the total branch support of the tree than adding extant taxa. This must be weighed against the superior taxon sampling afforded by including judiciously coded fossils, providing data from otherwise unsampled regions of the tree. We therefore recommend that investigators should include fossils, in the absence of compelling and case specific reasons for their exclusion.


The Pathergy Test as a Diagnostic Tool.
The pathergy test produces a nonspecific hyperreactive lesion in Behçet's disease (BD), a finding that has been known since 1937. Pathergy refers to the development of new skin lesions or the aggravation of existing ones after trivial trauma. In clinical practice, the pathergy test induces a skin response by needleprick, with positive reactions manifesting as a papule or pustule developing by 48 hours. The pathergy test is one of the major features and diagnostic criteria of the disease. It is very similar to the erythematous papules or pustules that appear spontaneously in patients with BD. There is no standardized method for conducting the pathergy test. Intradermal, intravenous, and subcutaneous applications are used. There is no generally accepted opinion on which form of the test yields a higher positivity rate. The pathergy reaction is also reported in pyoderma gangrenosum, and has been noted in other neutrophilic dermatoses such as Sweet syndrome. The overall objective of this contribution is to provide a review of the available information, literature, and research relating to the pathergy test.


Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients.
To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC). A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. In the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients. The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.


The effects of modality and elaboration on perceptual identification.
This paper describes two experiments on the effects of spoken and written priming on perceptual identification (visual word identification in Experiment 1 and auditory word identification in Experiment 2). Much previous work that has based the priming phase on the processing of word lists suggests that cross-modal priming (auditory-visual and visual-auditory) should be relatively weak. The present studies employed script- or story-based priming and represent a development on the earlier work by Carroll and Freebody (1987). In contrast to priming by list-processing, the reported findings show that homo-modal and cross-modal priming are indistinguishable, although only when the words are congruent with the story. Modality-shift effects are found when target words are incongruent with the stories in which they are found when target words are incongruent with the stories in which they are embedded at study. Results indicated that memory tests may be much more flexible with respect to the type of processing that can support performance than previous research suggests, and that the data-driven/conceptually driven distinction is not sufficient to account for the pattern of results obtained.


Nanohole arrays in chemical analysis: manufacturing methods and applications.
Since the last decade, nanohole arrays have emerged from an interesting optical phenomenon to the development of applications in photophysical studies, photovoltaics and as a sensing template for chemical and biological analyses. Numerous methodologies have been designed to manufacture nanohole arrays, including the use of focus ion beam milling, soft-imprint lithography, colloidal lithography and, more recently, modified nanosphere lithography (NSL). With NSL or colloidal lithography, the experimental conditions control the density of the nanosphere mask and, thus, the aspect of the nanohole arrays. Low surface coverage of the nanosphere mask produces disordered nanoholes. Ordered nanohole arrays are obtained with a densely packed nanosphere mask in combination with electrochemical deposition of the metal, glancing angle deposition (GLAD) or etching of the nanospheres prior to metal deposition. A review of these methodologies is presented here with an emphasis on the optical properties of nanoholes interesting in analytical chemistry. In particular, applications of these novel plasmonic materials will be demonstrated as substrates for a localized surface plasmon resonance (LSPR), Surface Plasmon Resonance (SPR), surface enhanced Raman spectroscopy (SERS), and in electrochemistry with nano-patterned electrodes.


Biochemical key to eight species of adult Egyptian mosquitoes.
1. An electrophoretic key is described, based on enzyme relative mobility, to distinguish eight species of Egyptian mosquito adults. 2. Using horizontal starch gel electrophoresis, five different enzyme assays unambiguously separated Culex pipiens L., Cx antennatus (Becker), Cx pusillus Macquart, Aedes caspius (Pallas), Culiseta longiareolata (Macquart), Uranotaenia unguiculata Edwards, Anopheles multicolor Cambouliu and An.pharoensis Theobald. 3. Diagnostic loci between species were: Ak-2, G6pd, alpha-Gpd, Gpi and 6-Pgd; the probability of correct diagnosis in each case was at least 0.989.


Health services utilization by fibromyalgia patients from two ethnic groups.
The cost to the healthcare system of management and treatment for fibromyalgia patients is high. The aims of the study were to identify and compare factors associated with the use of healthcare services among fibromyalgia patients in southern Israel from two ethnic groups. A cross-sectional study of patients insured in the southern district of the Clalit Healthcare Services in Israel in 2019-2020. The data were collected from the central computerized system. Multivariable regression models were developed for healthcare services utilization. During the study period, 7686 members were diagnosed with fibromyalgia. The median for specialist consultations was 47 and for imaging tests was eight. About 47% made emergency room visits and 25% were hospitalized. The median of imaging tests was significantly higher in Jewish patients than in Arab patients (8 vs. 6; p = .000). In contrast, a significantly higher rate of Arab patients visited the Emergency Room at least once (51.6% vs. 46.75%; p = .000) and they had a higher median number or Emergency Room visits (2 vs. 1; p = .003), compared with Jewish patients. In the Arab group there was a strong effect coefficient for another localized pain syndrome with specialist consultations (odds ratio [OR] 1.699; 95% confidence interval [CI] 1.266-2.241) and imaging tests (OR 2.511; 95% CI 1.496-4.146). The utilization rate of healthcare services is high among fibromyalgia patients. The factors associated with high healthcare utilization are different in the two ethnic groups. Future studies could show if interventions designed to address modifiable factors could reduce the overutilization of healthcare services.


[Proposal of standardised and logical templates for discharge letters and discharge summaries sent to general practitioners].
Background: Communication between general practitioners (GPs) and hospitals is a weak point of the French health system. Unfortunately, hospital discharge documents, a keypoint for healthcare safety and efficiency, tend to be poorly defined. This study aimed to propose standardised and logical templates for discharge letters (DL) and discharge summaries (DS) with particular attention to GPs' needs.Methods: A Delphi methodology was conducted on the findings of a systematic review of the international literature. We recruited 28 experts including producers (hospital physicians and interns), recipients (GPs, head of the medical information department, patient representatives), and other professionals using discharge documents (representative of regional health administration for inspection and control, jurist, pharmacists).Results: A consensus was reached after two rounds of consultation. According to the experts, DS should ideally be available on the last day of hospitalization, but this is rarely possible. DL have therefore become the most important document for GPs. Two standardised and logical templates were submitted to the experts for validation. The templates were considered to be pertinent by the experts and were perceived as improving several key points such as writing and reading speed, communication between hospitals and community practitioners or safety of healthcare after discharge from hospital.Conclusion: DL and DS templates will be tested in pilot hospitals by an impact study.


O-GlcNAcylation of BMAL1 regulates circadian rhythms in NIH3T3 fibroblasts.
Various physiological processes and behaviors show a circadian rhythm of approximately 24 h, which is crucial in coordinating internal metabolic processes and environmental signals. Post-translational modifications play an important role in regulating circadian core proteins. In this study, we demonstrated that BMAL1 was modified with an O-linked β-N-acetylglucosamine (O-GlcNAc), which stabilized BMAL1 and enhanced its transcriptional activity. Conversely, inhibition of O-GlcNAcylation resulted in inhibition of circadian rhythms of clock gene expression. Because O-GlcNAcylation is sensitive to the glucose level, such a modification may provide a new mechanism connecting metabolism with circadian rhythms.


In ovo vaccination of broilers against Campylobacter jejuni using a bacterin and subunit vaccine.
Campylobacter jejuni and Campylobacter coli originating from poultry meat have been the most important causes of foodborne bacterial gastroenteritis in the European Union since 2005. In-feed application of maternal antibodies from vaccinated hens was shown to confer protection of broilers against Campylobacter infection. Here, it was investigated if these vaccines can be used to protect broilers against Campylobacter infection after in ovo vaccination. Embryos were immunized in ovo at day 18 with a bacterin or a subunit vaccine and at 19 D post hatch, these birds were inoculated with C. jejuni according to a seeder model. Quantification of C. jejuni in the broilers cecal content showed that the in ovo vaccinated birds were not protected against C. jejuni infection. Quantification of blood anti-Campylobacter antibody titers did not show any induction of Campylobacter-specific serological response in the vaccinated birds, which may explain the lack of protection in the vaccinated chicks.


A Probe Into the Psychological Mechanism of Generation Z College Students Using Network Buzzwords in the Internet Era.
Network buzzwords are ubiquitous in the internet era. To explore the psychology of college students using network buzzwords, the development trend and characteristics of network buzzwords are analyzed first. A questionnaire survey is performed to learn how college students use network buzzwords currently; then, the obtained data are analyzed and discussed. Results demonstrate that 81.59% of college students can understand what the buzzwords mean. As for psychological factors, the average score of the identity dimension is the highest, and the average score of social support is the lowest. Among the behavioral factors, the communication factor scores the highest. Regarding the overall psychological and behavioral factors, in general, boys score higher than girls, and science and engineering students score higher than those majoring in literature, history, and art. Students of higher grades score lower than those of lower grades regarding using network buzzwords in communication and entertainment activities. The psychological mechanism of Generation Z college students using network buzzwords has been explored, which can provide scientific and practical reference materials for subsequent analysis and research on online behaviors of college students and is also of great significance for internet education of college students.


Cryosurgery for the urethral syndrome.
A technique is described for treating the urethral syndrome in ambulant women by cryosurgery under local anaesthesia using a specially devised guard or applicator. This follows a trial study (Parkes & Boreham 1980) in which a modified guard was used. Experience with over 350 cases and detailed follow up of 111 of them has confirmed improvement in 95% (93 of 111). No patient was made worse, only 10 required second treatments and the majority, when asked, said they thought the treatment was of value and that they would be prepared to have the same treatment again if necessary. This is a simple, safe and harmless technique for the treatment of the female urethral syndrome. It can be carried out under local anaesthesia as an outpatient or under general anaesthesia following cystoscopy. It causes few complications and relieves the symptoms in the majority of such patients.


Exploring and Exploiting the Effect of Solvent Treatment in Membrane Separations.
It is well-known that solvent treatment and preconditioning play an important role in rejection and flux performance of membranes due to solvent-induced swelling and solvent adsorption. Investigations into the effect of solvent treatment are scarce and application specific, and were limited to a few solvents only. This study reveals the trend in solvent treatment based on solvent polarity in a systematic investigation with the aim to harness such effect for intensification of membrane processes. Nine solvents with polarity indices ranging from 0.1 to 5.8 (hexane to acetonitrile) were used as treatment and process solvents on commercial Borsig GMT-oNF-2, Evonik Duramem 300, and emerging tailor-made polybenzimidazole membranes. TGA-GCMS, HS-GC-FID, and NMR techniques were employed to better understand the effect of solvent treatment on the polymer matrix of membranes. In this work, apart from the solvent treatment's direct effect on the membrane performance, a subsequent indirect effect on the ultimate separation process was observed. Consequently, a pharmaceutical case study employing chlorhexidine disinfectant and antiseptic was used to demonstrate the effect of solvent treatment on the nanofiltration-based purification. It is shown that treatment of polybenzimidazole membranes with acetone resulted in a 25% increase in product recovery at 99% impurity removal. The cost of the process intensification is negligible in terms of solvent consumption, mass intensity, and processing time.


[L-arginine and immunity. Study of pediatric subjects].
Nitric oxide (NO) play a pivotal role in many biological processes, as in the vessel tone control, the atherogenesis, the platelets aggregation and the immune system modulation. The physiologic precursor of NO is the L-arginine. Evidence exists that the L-arginine administration can stimulate immune system in children with recurrent infections. This clinical trial was designed to evaluate the effects of oral administration of L-arginine on the number of infective events and on the lymphocytes subsets in children suffering from airways recurrent infections. Forty outpatients, 21 male and 19 female, aging from 2 to 13 yrs. Two balanced groups, treated for 60 days with L-arginine or a placebo. Evaluation criteria: number of septic episodes; number of circulating white blood cells, % of the lymphocytes; lymphocytes subsets. Descriptive analysis; inference tests: chi 2; "t" test; variance analysis. Statistical significance: p = 0.05. Fifteen patients treated with L-arginine and five treated with placebo (p < 0.01) were free from infections. The percentage of CD3 and CD4 subsets significantly (p < 0.05) increased in the L-arginine group than in the placebo group, while the CD8 subset significantly decreased. The CD4/CD8 ratio raised from 1.05 +/- 0.29 to 1.51 +/- 0.46 (p < 0.01) in the L-arginine group, from 1.12 +/- 0.16 to 1.27 +/- 0.24 in the placebo group. There were no side effects in both groups. L-arginine seems able to increase the immune system defences and to protect against the airway infections.


Relationship between radiologist training level and fluoroscopy time for voiding cystourethrography.
The objective of our study was to determine whether voiding cystourethrography (VCUG) fluoroscopy time is related to the training level of the performing radiologist. VCUG reports with normal findings from 2008 to 2011 at one institution were retrospectively reviewed. The average fluoroscopy time was calculated for first-year radiology residents, senior radiology residents, pediatric radiology fellows, and attending pediatric radiologists. The average fluoroscopy time was also calculated for radiologist sex, patient sex, and patient age group. The analysis of variance was used to evaluate differences in average fluoroscopy times between training levels of radiologists, patient age groups, and patient sexes. We reviewed 784 VCUG reports with normal findings: 340 (43.4%) were performed by first-year residents; 181 (23%), by senior residents; 161 (20.5%), by fellows; and 102 (13%), by attending pediatric radiologists. The overall average fluoroscopy time was 1.86 minutes (SD ± 0.98). The attending pediatric radiologists had the shortest average fluoroscopy time (1.63 ± 0.92 minutes), significantly shorter than senior residents (1.96 ± 1.09 minutes; p = 0.0070) and fellows (1.91 ± 0.85 minutes; p = 0.0255). There was no significant difference between attending radiologists and first-year residents (1.85 ± 1.00 minutes; p = 0.0550). The male-to-female ratio of radiologists was 54% versus 46%, with identical average fluoroscopy times: male radiologists, 1.86 ± 1.05 minutes; female radiologists, 1.86 ± 0.90 minutes. There was no significant difference in average fluoroscopy times among patient age groups: 1.93, 1.76, and 1.78 minutes, respectively, for groups A (0-1 years), B (> 1 to ≤ 5 years), and C (> 5 years) (p = 0.1750, 0.4605, 0.6303). The average fluoroscopy time for male patients (2.02 ± 1.00 minutes) was significantly longer than that for female patients (1.71 ± 0.95 minutes; p < 0.0001). Attending pediatric radiologists have the shortest fluoroscopy time; the differences between their average time compared with the average times of pediatric radiology fellows and of senior radiology residents were statistically significant. The average fluoroscopy time is longer for male patients than for female patients.


Family Structure is Associated with Mental Health and Attention Deficit (Hyperactivity) Disorders in Adolescents with Type 1 Diabetes.
To analyze the cross-sectional associations of family structure with mental health and attention deficit (hyperactivity) disorders (AD(H)D) in 11- to 17-year-old adolescents with early-onset type 1 diabetes participating in one of three baseline surveys as part of an ongoing cohort study. Parents (n=1,631) completed the Strengths and Difficulties Questionnaire to screen for their child's mental health and answered questions about their child's diagnosis of AD(H)D. Associations between mental health or AD(H)D and family structure were analyzed using multivariable logistic regression analyses adjusted for various personal and diabetes-related variables. Compared to adolescents living with both parents, adolescents living with one parent and his/her partner had 2.35 (95% confidence interval 1.32; 4.21) higher odds of abnormal screening result and 2.08 (1.09; 3.95) higher odds of a borderline screening result while adolescents living with a single parent had 1.84 (1.07; 3.17)/1.08 (0.53; 2.21) higher odds of abnormal/borderline screening results. The odds ratios for diagnosed attention deficit (hyperactivity) disorder were 2.17 (0.98; 4.84) for adolescents living with one parent and his/her partner and 1.27 (0.54; 3.01) for those living with a single parent vs. both parents. Our results indicate higher odds of mental health problems and AD(H)D in adolescents with type 1 diabetes who do not live with both parents; this finding was most pronounced in individuals living with one parent and his/her partner vs. both parents. Longitudinal studies are needed to verify our results and elucidate the underlying mechanisms.


Introduction to economic assessment - part 4.
This is the final in a series of four continuing professional development articles on economic assessment (EA), more specifically EA in the context of nurse-led service innovation. The series aims to equip readers with an understanding of: (a) the main requirements of EA; (b) definitions of relevant terminology; (c) different EA techniques and their associated strengths and weaknesses; and (d) procedures to assign monetary values to costs and benefits. The series introduces a methodology, with associated tools and templates, that has been used by practising nurses to conduct EAs. The aim of this article is to show readers how to put monetary values on the types of cost incurred, and benefits generated, by a service innovation.


Weighting genomic and genealogical information for genetic parameter estimation and breeding value prediction in tropical beef cattle.
A combined matrix that exploits genealogy together with marker-based information could improve the selection of elite individuals in breeding programs. We present genetic parameters for adaptive and growth traits in beef cattle by exploring linear combinations of pedigree-based (A) and marker-based (G) relationship matrices. We use a data set with 2,111 Brahman (BB) and 2,550 Tropical Composite (TC) cattle with genotypes for 729,068 SNP, and phenotypes for five traits. A weighted relationship matrix (WRM) combining G and A was constructed as WRM = λG + (1 - λ)A. The weight (λ) was explored at values from 0.0 to 1.0, at 0.1 intervals. Additionally, four alternative G matrices, in the WRM, were evaluated according to the selection of SNP used to generate them: 1) Gw: all autosomal SNP with minor allele frequency (MAF) > 1%; 2) Gg: autosomal SNP with MAF > 1% and mapped inside to gene coding regions; 3) Gp: autosomal SNP with MAF > 1% and previously reported to have significant pleiotropic effect in these two populations; and 4) Gc: autosomal SNP with MAF > 1% and with significant correlated effects previously reported in both BB and TC populations. In addition, two A matrices were evaluated: 1) A: all relationships between animals were considered after tracing back known ancestors; and 2) Ad: a distorted A matrix where a random 1% of the off-diagonal nonzero values were set to zero to simulate relationship errors. Five independent Ad matrices were explored each with a different random 1% of relationships masked. Criteria for comparing the resulting WRM included estimates of heritability (h2) and cross-validation accuracy (ACC) of genomic estimated breeding values. The choice of WRM had a greater impact on h2 than on ACC estimates. The 1% errors introduced in pedigree relationships generated large distortion in genetic parameters and ACC estimates. However, employing a λ > 0.7 was an efficient mechanism to compensate for the errors in A. Additionally, although significant (P-value < 0.0001), we found no consistent relationship between the type of SNP used to compute G and h2 or ACC estimates. We devised the optimal value of λ for maximum h2 and ACC at λ = 0.7 suggesting a 70% and 30% weighting to genomic and genealogical information, respectively, as an optimal strategy to compensate for pedigree errors, to improve genetic parameters estimates and lead to more accurate selection decisions.


The role of mesenchymal stem cell-derived EVs in diabetic wound healing.
Diabetic foot is one of the most common complications of diabetes, requiring repeated surgical interventions and leading to amputation. In the absence of effective drugs, new treatments need to be explored. Previous studies have found that stem cell transplantation can promote the healing of chronic diabetic wounds. However, safety issues have limited the clinical application of this technique. Recently, the performance of mesenchymal stem cells after transplantation has been increasingly attributed to their production of exocrine functional derivatives such as extracellular vesicles (EVs), cytokines, and cell-conditioned media. EVs contain a variety of cellular molecules, including RNA, DNA and proteins, which facilitate the exchange of information between cells. EVs have several advantages over parental stem cells, including a high safety profile, no immune response, fewer ethical concerns, and a reduced likelihood of embolism formation and carcinogenesis. In this paper, we summarize the current knowledge of mesenchymal stem cell-derived EVs in accelerating diabetic wound healing, as well as their potential clinic applications.


Effect of muscle opposition during rigor on development of broiler breast meat tenderness.
Two experiments were conducted to determine the effect of mutual opposition of breast muscles during rigor development on ultimate tenderness of the cooked meat. In each experiment, 32 broilers were conventionally processed. Immediately after evisceration, the supracoracoideus tendon was cut at the humeral insertion on one wing (treatment) and the opposite wing was sham-operated with the tendon exposed but not cut (control). The tendon of insertion for the Pectoralis minor muscle was cut to prevent the opposition of breast muscles during rigor, while avoiding confounding effects caused by making cuts on the muscles, as would occur during typical deboning. Cutting the tendon significantly (P < 0.05) increased Warner-Bratzler shear values after cooking for both the Pectoralis major and P. minor. Deboning at 2 h post-mortem resulted in shear values for the P. major of 7.22 kg for controls and 9.08 kg for treated carcasses; P. minor shear values were 2.98 kg for controls and 4.04 kg for treated carcasses. Deboning at 24 h post-mortem produced P. major shear values of 4.68 kg for controls and 5.68 kg for treated carcasses. On whole carcasses, breast muscle opposition during rigor contributes to the tenderness of the cooked meat.


Mouse testicular sulfated glycoprotein-1: sequence analysis of the common backbone structure of prosaposins.
We have generated a cDNA encoding the mouse sulfated glycoprotein-1 (SGP-1) by polymerase chain reaction amplification of a mouse testicular Uni-Zap XR cDNA library with two synthetic oligonucleotide primers. A positive signal of 1,959 bases was isolated and subcloned into the pGEM-T. Sequence analysis showed a near identical nucleotide and amino acid similarity to mouse prosaposin cDNA. A few amino acid differences were found, and they may represent strain-specific heterogeneities. The cDNA has 88% amino acid identity to rat SGP-1 and 64% identity to human prosaposin. Prosaposin is the precursor of four lysosomal saposins (A, B, C, and D) that are generated by the proteolytic maturation of the former. Saposins are sphingolipid binding proteins that function as activators of lysosomal enzymes involved in sphingolipid hydrolysis. Northern blot analysis demonstrated that SGP-1 mRNA is transcribed in the seminiferous epithelium by Sertoli cells but not by germinal cells. Our results also demonstrated two forms of alternatively spliced testicular SGP-1 mRNA. This alternative splicing results in the inclusion or exclusion of exon 8, which encodes for three amino acid residues (QDQ) that are implicated in the sphingolipid binding affinity of saposin B. Sequence aligment indicates that all saposins share a common motif characterized by six conserved cysteines, a conserved N-linked glycosylation site, a conserved proline residue, and 15 positions that are characterized by large hydrophobic amino acids. These characteristics, together with similar secondary structure predictions and the predicted similar formation of three disulfide linkages, create a common framework of amino acids of three alpha helices enclosing an internal hydrophobic core for all saposins. The disulfide placement data, the hydropathy profile, and the presence of amphiphatic helices indicate that all saposins are stable proteins sharing similar secondary and tertiary structures.


[Are blood tests prior to ear operations in children necessary?--A retrospective analysis].
Operations in children are often drastic events for patients and their parents. Most ENT operations are elective. Often blood tests are done even though there is no clinical evidence for coagulation disorders or anaemia in the medical history of the patient and their family. Since the joint statement of the German Societies of Oto-Rhino-Laryngology, Head and Neck surgery, of pediatrics and of anesthesiology regarding the necessity of coagulation tests prior to adenoidectomy or tonsillectomy in children we wanted to know whether blood tests have any effect for ear operations. Data of 81 children were analysed, undergoing an ear operation during 2006/2007 at the department of Oto-Rhino-Laryngology in Bochum, retrospectively. Information on sex, age, hemoglobin concentration, platelet count, INR, thromboplastin time, prothrombin time, count of the white blood cells, Cholinesterase (CHE), Glutamat-Oxalacetat-Transaminase (GOT), Glutamat-Pyruvat-Transaminase (GPT), gamma-Glutamyltransferase (GT), Creatinkinase (CK), creatinine, c-reactive protein (CRP) and clinical history of postoperative complications (bleeding, infections) were collected. Out of 698 registered parameters 10,5 % were differing from the reference parameters. There were no abnormal bleedings or complications which could have been predicted by blood tests. The preoperative blood tests have no influence on the management of an elective ear operation. A thorough medical patient's and family history should be taken and may be added by a calculated analysis of special blood tests.


Prognostic factors of time to first abortion after sexual debut among fragile state Congolese women: a survival analysis.
Despite the common restrictive abortion laws, abortion remains widespread in sub-Saharan Africa (SSA) countries. Women still utilize abortion services and put their lives and health at risk because abortion can only be procured illegally in private facilities such as mid-level or small patent medicine store that may be manned by unskilled providers or through a non-medicated approach. The objective of this study was to investigate the prevalence of abortion, the reasons women had abortions, median years to first abortion after sexual debut and examine the factors of time to first abortion among women of reproductive age in the Republic of Congo. We used data from the most recent Republic of Congo Demographic and Health Survey (DHS). A total sample of 3622 women aged 15-49 years was analyzed. We estimated the overall prevalence of abortion and median years to first abortion. Furthermore, we examined the factors of time to first abortion after sexual debut using multivariable Cox regression and reported the estimates using adjusted Hazard Ratio (aHR) and 95% confidence intervals (CI). Statistical significance was determined at p < 0.05. The prevalence of abortion was 60.0% and median years of time to first abortion after sexual debut was 9.0. The prominent reasons for abortion were due to too short birth interval (23.8%), lack of money (21.0%) and that husband/partner did not need a child at that time (14.0%). Women's age and region were notable factors in timing to first abortion. Furthermore, women from poorer, middle, richer and richest households had 34, 67, 86 and 94% higher risk of abortion respectively, when compared with women from poorest households (all p < 0.05). Women currently in union/living with a man and formerly in union had 41 and 29% reduction in the risk of abortion respectively, when compared with those never in union (all p < 0.05). In addition, women with primary and secondary+ education had 42 and 76% higher risk of abortion respectively, when compared with women with no formal education (all p < 0.05). There was high prevalence of abortion with short years at first abortion. Abortion was associated with women's characteristics. There is need for unwanted pregnancy prevention intervention and the improvement in pregnancy care to reduce adverse pregnancy outcomes among women.


Sensitivity of stretch-activated K+ channels changes during cell-cleavage cycle and may be regulated by cAMP-dependent protein kinase.
The properties of stretch-activated K+ channels in the membrane of loach (Misgurnus fossilis) embryos were studied using the patch-clamp technique. It was found that in the early stages of embryogenesis (2-256 cells) the stretch sensitivity of stretch-activated (SA) channels changes dramatically during the cell cleavage cycle. At the beginning of interphase the stretch sensitivity of SA channels and the probability of being in the open state (P0) were minimal, whereas at prometaphase they were increased 10-100-fold. Application of ATP to the cytoplasmic surface of excised inside-out patches induced a reversible increase in resting P0 and of stretch sensitivity of the SA channels in 50% of the patches, but the non-hydrolysable analogue of ATP, 5'-adenylylimidodiphosphate (AMP-PNP), was not effective. Phosphatase inhibitors (orthovanadate and para-nitrophenyl phosphate) prolonged the effect of ATP. Combined application of ATP, cAMP and cAMP-dependent protein kinase (PK) induced a reversible increase in the SA channel activity in 70% of those excised patches which did not respond to ATP. Inhibitors of PK prevented its activating effect. Dibutyryl-cAMP (dB cAMP) transiently increased activity of SA channels in intact cells. These results suggest that activity of SA channels may be regulated through cAMP-dependent phosphorylation and thus provide the basis for explanation of stretch sensitivity modulation during the cell cycle.


The second component of human complement: its isolation, fragmentation by C'1 esterase, and incorporation into C'3 convertase.
A method has been described for the purification and isolation of the second component of complement (C'2) from human serum. The protein is a beta(1)-globulin with an approximate molecular weight of 117,000. Immunochemical analysis using a variety of specific antisera, including a monospecific antiserum to the isolated protein, indicate that the C'2 protein represents a heretofore unrecognized human serum constituent. Isolated C'2 contained 2 x 10(9) "effective molecules" per microgram and 1000 hemolytically active C'2 molecules were required to produce a single hemolytically effective C'2 site on erythrocytes undergoing immune cytolysis. C'1 esterase treatment of C'2 resulted in reduction of both its electrophoretic mobility and its molecular size, the latter observation indicating fragmentation of the molecule. Direct evidence was presented for the physical presence of C'2 as an integral part of the enzyme C'3 convertase.


The influence of electrical effects on device performance of organic solar cells with nano-structured electrodes.
Integration of light-trapping features and exploitation of metal nanostructure plasmonic effects are promising approaches for enhancing the power conversion efficiency of organic solar cells. These approaches' effects on the light absorption enhancement have been widely studied, especially in inorganic devices. While this light-trapping concept can be transferred to organic devices, one has to also consider nanostructure-induced electrical effects on the device performance, due to the fundamental difference in the organic semiconducting material properties compared to their inorganic counterparts. In this contribution, we exemplarily model the electrical properties of organic solar cells with rectangular-grating structures, as compared to planar reference devices. Based on our numeric results, we demonstrate that, beyond an optical absorption enhancement, the device fill factor improves significantly by introducing the grating structures. From the simulations we conclude that enhanced carrier collection efficiency is the main reason for the increased solar cell fill factor. This work contributes towards a more fundamental understanding of the effect of nanostructured electrodes on the electrical properties of organic solar cells.


A near-complete genome assembly of Catharanthus roseus and insights into its vinblastine biosynthesis and high susceptibility to the Huanglongbing pathogen.
This study reports the assembly of a near-complete genome of Catharanthus roseus, consisting of 561.7 Mb scaffolded into 8 pseudochromosomes with a contig N50 of 24.7 Mb and a scaffold N50 of 71.1 Mb. The assembly enables the construction of a gene regulatory network of the vinblastine biosynthetic pathway and provides insights into the high susceptibility of C. roseus to the Huanglongbing pathogen.


Ethic and patents: immiscible realities?
Intellectual Property ("IP") protection of the results of proteomics, genomics and other aspects of biomedical research can lead to significant issues and concerns. Some of these include whether (a) IP protection will impede research into future breakthroughs, (b) IP protection will increase the costs or decrease the access to new therapies or treatment modalities and (c) whether and how IP protection should recognize indigenous knowledge and genetic resources. As the chorus of apprehension is growing, this article will explore the issues and concerns raised by the intersection of new technologies and traditional IP protection.


Time trend analysis of otological procedures performed in England, 1989 to 2005.
To observe trends in the number of major otological procedures performed in England, in the context of advances in the understanding of disease. The data used were obtained from the Hospital Episode Statistics statistical database, published by the UK Department of Health, for England, 1989 to 2005. Specific otological procedures were identified using the Classification of Surgical Operations and Procedures system (fourth revision) of the Office of Population, Censuses and Surveys. Trend analysis of different procedures was performed using exponential smoothing (using the Statistical Package for the Social Sciences version 13 software). Our study did not confirm any reduction in the number of surgical procedures performed for cholesteatoma or otosclerosis. We noted a sharp decline in the number of endolymphatic sac surgical procedures performed, probably attributable to the increased use of intratympanic therapy. The number of major otological procedures (other than endolymphatic sac surgery) was consistent over the period examined. The generally perceived reduction in the number of procedures performed by individual surgeons may be due to a dilutional effect. This can only support the need for subspecialisation, particularly regarding the training of junior surgeons.


Recurrent giant cellulitis-like Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine.
Primary and booster vaccines for SARS-CoV-2 are the most effective methods of preventing infection and are generally considered safe. However, many cutaneous adverse events have been reported following vaccination. To date, there have been seven reported cases of Sweet syndrome occurring after the first dose of the SARS-CoV-2 vaccine. We describe a rare case of atypical giant-cellulitis like Sweet syndrome reemerging after receiving the SARS-CoV-2 booster vaccine.


De-silencing Grb10 contributes to acute ER stress-induced steatosis in mouse liver.
The growth factor receptor bound protein GRB10 is an imprinted gene product and a key negative regulator of the insulin, IGF1 and mTORC1 signaling pathways. GRB10 is highly expressed in mouse fetal liver but almost completely silenced in adult mice, suggesting a potential detrimental role of this protein in adult liver function. Here we show that the Grb10 gene could be reactivated in adult mouse liver by acute endoplasmic reticulum stress (ER stress) such as tunicamycin or a short-term high-fat diet (HFD) challenge, concurrently with increased unfolded protein response (UPR) and hepatosteatosis. Lipogenic gene expression and acute ER stress-induced hepatosteatosis were significantly suppressed in the liver of the liver-specific GRB10 knockout mice, uncovering a key role of Grb10 reactivation in acute ER stress-induced hepatic lipid dysregulation. Mechanically, acute ER stress induces Grb10 reactivation via an ATF4-mediated increase in Grb10 gene transcription. Our study demonstrates for the first time that the silenced Grb10 gene can be reactivated by acute ER stress and its reactivation plays an important role in the early development of hepatic steatosis.


Evaluation of cytotoxic effects of several novel tetralin derivatives against Hela, MDA-MB-468, and MCF-7 cancer cells.
The inhibitors of the enzymes estrone sulfatase and 17-β-hydroxysteroid dehydrogenase (17-β-HSD) could provide a means of blocking estrogen biosynthesis leading to regression of estrogen-dependent tumors. We evaluated the cytotoxicity of several tetralin derivatives, 2-(4-halo-phenylmethylene)-3,4-dihydronaphthalene-1-ones, as potential inhibitors of these two enzymes, on Hela, MDA-MB-468, and MCF-7 cancer cell lines. The cell lines were cultured in RPMI medium and the cytotoxic effect of tested compounds (compounds 1 to 5) was screened at the concentrations of 0.1, 1, and 10 μM either alone or in combination with doxorubicin (100 μM), using MTT assay. The mixtures of cell suspension with solvent (1% DMSO in PBS) and doxorubicin (100 μM) were used as negative and positive controls, respectively. Each concentration of compounds was assayed in four wells and repeated in at least three independent experiments for each cell line. The cytotoxic effect of each particular concentration of tested compounds was expressed as the percent of cell survival. None of the compounds exhibited cytotoxic effect (reduction of cell survival to less than 50%) on tested cell lines. However, statistically significant reduction in cell survival was observed for some compounds against particular cell lines. Among all tested combinations of compounds with doxorubicin against cell lines, only compound 4 at 10 μM concentration showed synergistic cytotoxic effect with doxorubicin against Hela cells. With the exception of compound 2, other tested compounds have potential for further cytotoxicity evaluation. Synthesizing other tetralin derivatives similar to compound 4 and studying their structure-activity relationships (SARs) would be encouraged.


Interaction between asthma and smoking increases the risk of adult airway obstruction.
The aim of the present study was to analyse the interaction between asthma and smoking in the risk of adult airway obstruction, accounting for atopy. In the European Community Respiratory Health Survey, 15 668 persons aged 20-56 years underwent spirometry in 1991-1993 and 9 years later (n=8916). Risk of airway obstruction and lung function decline associated with smoking and early-onset (<10 years of age) and late-onset (>10 years of age) asthma were analysed with generalised estimating equation models and random-effect linear models, adjusting for covariates. Interaction of asthma with smoking was expressed as relative excess risk due to interaction (RERI). A 20-fold increase in adult airway obstruction was found among those with early-onset asthma independently of smoking status (never-smokers: OR 21.0, 95% CI 12.7-35; current smokers: OR 23.7, 95% CI 13.9-40.6). Late-onset asthma was associated with airway obstruction, with a stronger association among current smokers (OR 25.6, 95% CI 15.6-41.9) than among never-smokers (OR 11.2, 95% CI 6.8-18.6) (RERI 12.02, 95% CI 1.96-22.07). Stratifying by atopy, the association between smoking and asthma was most pronounced among nonatopics. Early- and late-onset asthma were associated with 10-20-fold increased risk of adult airway obstruction. Smoking increased the risk of adult airway obstruction in subjects with asthma onset after age 10 years. Investigation of measures potentially preventive of chronic obstructive pulmonary disease development following asthma is urgently needed.


Ligand-to-Ligand Charge Transfer within Metal-Organic Frameworks Based on Manganese Coordination Polymers with Tetrathiafulvalene-Bicarboxylate and Bipyridine Ligands.
A systematic study on ligand-to-ligand charge-transfer (LLCT) properties of three closely related metal-organic frameworks (MOFs) is presented. These compounds are formulated as [MnL(4,4'-bpy)(H2O)]n·nCH3CN (1), [MnL(bpe)0.5(DMF)]n·2nH2O (2), and [MnL(bpa)(H2O)]n·2nH2O (3) (L = dimethylthio-tetrathiafulvalene-bicarboxylate, 4,4'-bpy = 4,4'-bipyridine, bpe = 1,2-bis(4-pyridyl)ethene, bpa = 1,2-bis(4-pyridyl)ethane). The X-ray single-crystal diffractions show that complexes 1-3 are all two-dimensional (2-D) coordination polymers with different frameworks in crystal lattices. Charge-transfer (CT) interactions within these MOFs are visually apparent in colors and vary according to the conjugated states of the bipyridine ligands (4,4'-bpy, bpe, and bpa). Theoretical calculations show that the charge transfer occurs from ligand L to bipyridine. The intensity of the LLCT is in the order of 2 > 1 > 3 investigated by theoretical calculations and ESR, which indicates that the intensity of CT is related to the bipyridyl conjugated state. Photocurrent responses of these compounds are consequently studied, and the results are in agreement with the intensity of charge transfer and linearly related to the LLCT energy.


Carcinoma of the renal pelvis and ureter.
To assess the occurrence of upper urinary tract urothelial tumors (UUTT) in Brazil. We performed a clinical and histopathologic study of 33 patients who were diagnosed with a malignant neoplasm in the renal pelvis or ureter in the period of 1994 to 2004, in a single institution. Among the patients with upper urinary tract carcinoma, 70% were males and 30% females, with mean age of 65 +/- 16 years (ranging from 31 to 91 years). Nineteen patients presented renal pelvis tumor (58%), 9 ureteral tumor (27%) and 5 synchronic pelvic and ureteral tumors (15%). Renal pelvis tumors represented 2.8% of all the urothelial neoplasms, and 11.4% of all renal neoplasms treated in the same period. Ureteral tumors represented 1.6% of all the urothelial malignancies surgically managed in these 11 years. Tobacco smoking was the most common risk factor, and analgesic abuse was not reported by those patients. Most carcinomas were high-grade and muscle-invasive. Mean time to diagnosis was 7 months, being hematuria the most common symptom. A high association was also found between UUTT and bladder urothelial carcinoma. UUTT were mostly seen in men in their seventies and related to a high overall and cancer-related mortality rate. The overall disease-specific survival was 40%, much lower than found in most of the reported series.


Religiosity and Health Through the Decades: Is There a Gender Difference?
An empirical examination of the long-term association, disaggregated by gender, between religiosity and self-rated health with reference to demographic shifts in labor force participation, education, and income. General Social Survey data. United States, 1974 to 2012. A total of 23 353 respondents. Self-assessed health; 2 key religiosity variables: attendance and intensity of belief; income, labor market variables, education, standard demographic variables, household size, region, and time dummies. Probit estimation conducted for the aggregate sample by gender as well as by decades to examine possible gender differential changes over time. Attendance has declined overall with a much greater decline for women. The overall positive association between religiosity and health masks considerable heterogeneity across gender and time; higher and stable for males, there is no longer a significant association for females. Increased education, income, and labor force participation can explain only part of this association. Education is the strongest mediator. The way women and men benefit from religious attendance has changed, suggesting that some pathways may be working differently for women now, especially those with less education. Moving away from church networks could be due to a perceived lack of support or substitution by other social networks. Ceteris paribus, since religious participation has been shown to weaken preference for risky consumption, declining participation, especially for women, may show up as an increase in risky behavior.


Scent through the looking glass.
In 1896, Tiemann first raised the question of whether or not enantiomers might exhibit different odors. The classic work of von Braun should have settled the issue in 1927 but the debate continued for decades, often rather acrimoniously. Various factors such as purity of samples and subjectivity of odors provided the confusion necessary to perpetuate disagreement. Nowadays, we have enough good-quality data to know that sometimes, absolute configuration affects odor perception and sometimes it does not. We are, therefore, left with some interesting academic and commercial questions to be addressed.


Alteration of cardiovascular, neurogenic, and humoral responses to acute hypovolemic hypotension by administered prostacyclin.
Acute hypovolemia induced by bleeding (5 ml/300 g body weight) halothane-anesthetized (0.8% in oxygen) rats is attended by hypotension, bradycardia, and increases in plasma renin, vasopressin, and catecholamine levels. Infusion of prostacyclin (PGI2, O.03 microgram/kg.min) to acutely hemorrhaged rats enhanced recuperation of heart rate, and potentiated the sympathetic response and vasopressin release without altering blood pressure of plasma renin concentration (PRC). Bleeding of bilaterally adrenal demedullated, splanchnicectomized rats resulted in prolonged hypotension and increased plasma levels of vasopressin and renin; epinephrine in the plasma was not detectable, and plasma norepinephrine concentration was not increased after hemorrhage. Prostacyclin infusion to the demedullated, splanchnicectomized rats had no effect on heart rate but enhanced blood pressure recovery after hemorrhage; in this experimental group, PRC was markedly elevated but prostacyclin had no effect on plasma vasopressin or catecholamine concentrations. In rats exposed to severe bleeding, resulting in a nonreversible shock and high mortality, PGI2 infusion after the bleeding increased the survival rate without effect on blood pressure, heart rate, or circulating levels of vasopressin and catecholamines. This study suggests that prostacyclin, through stimulation of the sympathoadrenal axis, enhances heart rate recuperation and vasopressin release in response to acute hemorrhagic shock. Furthermore, prostacyclin may stimulate renin secretion in sufficient amount to compensate for the inadequate sympathetic response during hemorrhagic shock. It is also shown that prostacyclin improves the survival rate to severe hemorrhage without overt hemodynamic or sympathetic effects.


The perception of temporal modulations by cochlear implant patients.
The perception of temporal modulations of pulsatile electric stimuli was measured in seven cochlear implant patients using the Cochlear Pty. Limited prosthesis. Four patients were postlingually deafened adults and three patients were young adults who were deafened very early in life. The first study measured detection thresholds for modulated pulse duration for a series of modulation frequencies and pulse rates. The shape of the detection thresholds as a function of modulation frequency, the temporal modulation transfer function, often resembled a low-pass filter with a 50-100-Hz cut-off frequency. Thresholds did not markedly vary across the different pulse rates for most patients. Thresholds were less than 10%-20% of the range of usable hearing for most patients. The second study compared detection thresholds for modulated pulse durations around different reference pulse durations: 50, 100, and 300 microseconds. Detection thresholds were generally proportional to the different reference pulse durations. The third study measured difference limens for the discrimination of modulation depth. The difference limens were similar to the detection thresholds for the same reference pulse duration and pulse rate. The three patients deafened very early in life showed more within-group variation in performance, and their overall levels of performance were poorer than those of the postlingually deafened adults.


Role of endothelin-1 and its receptors, ETA and ETB, in the survival of human vascular endothelial cells.
Our previous work showed the presence of endothelin-1 (ET-1) receptors, ETA and ETB, in human vascular endothelial cells (hVECs). In this study, we wanted to verify whether ET-1 plays a role in the survival of hVECs via the activation of its receptors ETA and (or) ETB (ETAR and ETBR, respectively). Our results showed that treatment of hVECs with ET-1 prevented apoptosis induced by genistein, an effect that was mimicked by treatment with ETBR-specific agonist IRL1620. Furthermore, blockade of ETBR with the selective ETBR antagonist A-192621 prevented the anti-apoptotic effect of ET-1 in hVECs. However, activation of ETA receptor alone did not seem to contribute to the anti-apoptotic effect of ET-1. In addition, the anti-apoptotic effect of ETBR was found to be associated with caspase 3 inhibition and does not depend on the density of this type of receptor. In conclusion, our results showed that ET-1 possesses an anti-apoptotic effect in hVECs and that this effect is mediated, to a great extent, via the activation of ETBR. This study revealed a new role for ETBR in the survival of hVECs.


Why did adolescents have sleep problems after earthquakes? Understanding the role of traumatic exposure, fear, and PTSD.
To examine the relationships between trauma exposure, fear, post-traumatic stress disorder, and sleep problems in adolescents, 746 adolescent survivors of the 2008 Wenchuan earthquake in China were assessed at 1 year (T1) and 1.5 years (T2) after the earthquake using a trauma exposure questionnaire, a fear questionnaire, a child posttraumatic stress disorder symptom scale, and a subscale on child sleep problems. The results showed that T1 trauma exposure were not directly associated with sleep problems at T1 and T2, but played a positive role in sleep problems at both T1 and T2 indirectly through T1 posttraumatic stress disorder and T1 fear. T1 trauma exposure was also positively and indirectly associated with T2 sleep problems through T1 posttraumatic stress disorder via T1 sleep problems, or through T1 fear via the path from T1 posttraumatic stress disorder to T1 sleep problems. These findings indicated that fear and posttraumatic stress disorder 1 year after the earthquake played a mediating role in the relationship between trauma exposure at 1 year after the earthquake, and sleep problems at both 1 year and 1.5 years after the earthquake, respectively. In particular, posttraumatic stress disorder also had a multiple mediating effect in the path from trauma exposure to sleep problems via fear. Furthermore, the findings indicated that sleep problems were relatively stable between 1 and 1.5 years after an earthquake.


Enhanced secondary metabolite (tanshinone) production of Salvia miltiorrhiza hairy roots in a novel root-bacteria coculture process.
Salvia miltiorrhiza Bunge (Lamiaceae) hairy root cultures were inoculated (at 0.02 and 0.2% v/v) and co-cultured with Bacillus cereus bacteria. The root biomass growth was inhibited significantly by the bacteria inoculated to the root culture on the first day (day 0) but not by the bacteria inoculated on days 14 or 21 (in a 28-day overall period). On the other hand, the growth of the bacteria in the hairy root culture was also strongly inhibited by the hairy roots, partially because of the antibacterial activity of the secondary compounds produced by the roots. Most interestingly, the tanshinone production was promoted by the inoculation of bacteria at any of these days but more significantly by an earlier bacteria inoculation. With 0.2% bacteria inoculated on day 0, for example, the total tanshinone content of roots was increased by more than 12-fold (from 0.20 to 2.67 mg g(-1) dry weight), and the volumetric tanshinone yield increased by more than sixfold (from 1.40 to 10.4 mg l(-1)). The tanshinone production was also stimulated by bacterial water extract and bacterial culture supernatant but less significantly than by the inoculation of live bacteria. The results suggest that the stimulation of tanshinone production by live bacteria in the root cultures may be attributed to the elicitor compounds originating from the bacteria, and the hairy root-bacteria coculture may be an effective strategy for improving secondary metabolite production in plant tissue cultures.


Increasing dietary protein acutely augments intestinal iron transporter expression and significantly increases iron absorption in rats.
Iron (Fe) deficiency is endemic worldwide. Little data are available regarding acute effects of dietary protein on intestinal Fe absorption. The current study evaluated the short-term effects of increasing dietary protein on Fe absorption and expression of genes involved in Fe homeostasis. Sprague Dawley rats (24, female) were randomly assigned to custom-formulated isocaloric diets containing 40, 20 (control), or 5% protein (as percentage of total kilocalories) for 7 d. Whole-body Fe balance studies demonstrated that Fe retention was greater in the 40% group than in the 5% group (30.8 vs. 7.3%; P<0.01). In a separate study utilizing stable iron isotopes, the 40% group absorbed 30% of ingested Fe, while the 20% group absorbed 18% (P=0.005). Whole-genome profiling revealed that increasing dietary protein from 5 to 40% increased duodenal transcript expression of divalent metal transporter 1 (DMT1) 3.2-fold, duodenal cytochrome b (Dcytb) 1.8-fold, and transferrin receptor (TfR) 1.8-fold. Consistent with these findings, DMT1 transcript expression was 4-fold higher in RNA prepared from duodenal mucosa in the 40% group compared to the 20% group (P<0.001). These data suggest that increasing dietary protein increases intestinal Fe absorption in part by up-regulating DMT1, Dcytb, and TfR.


Concha bullosa mucocele: A case series and review of the literature.
Concha bullosa mucocele is a rare diagnosis that presents as a nasal mass. It impinges on surrounding structures and can easily be mistaken for a neoplasm. The objective of this study was to shed light on this rare entity and report its diagnostic features and treatment outcomes. A case series conducted in a tertiary health care center. Demographic data, clinical presentation, imaging, cultures, and treatments were recorded. Operative video illustration and key images were obtained. A review of the literature was also performed. A total of five cases were reviewed, four of which were concha bullosa mucoceles and one was a mucopyocele. Three of the patients had some form of previous nasal trauma. Headache and nasal obstruction were the most common symptoms with a nasal mass finding on physical examination. Computed tomography was used in all the patients, and magnetic resonance imaging was used in four of the five patients. Four patients had coexistent chronic rhinosinusitis, and three had positive bacterial cultures. All these patients were treated endoscopically either with middle turbinate marsupialization or subtotal resection. No recurrence has been noted thus far. Concha bullosa mucocele is a rare diagnosis. Imaging characteristics are helpful in considering the diagnosis, although surgical intervention is often necessary to confirm the diagnosis and treat concha bullosa mucocele.


A Meta-Analysis for Effects of Elevated Pre-Transplantation Serum Ferritin on the Outcomes in Patients Undergoing Hematopoietic Stem Cell Transplantation.
The level of pre-transplantation serum ferritin (SF) is one of the factors related to outcome for patients undergoing allogeneic hematopoietic stem cell transplantation. We searched PubMed and Cochrane Library databases from 2000 to 2014. The primary efficacy outcome was overall survival rate and non-relapse mortality. Twenty clinical trials were selected from 189 studies identified. The combined hazard ratio indicated a significantly lower overall survival rate and a higher non-relapse mortality rate in patients with elevated SF before transplantation. This indicates that elevated pre-transplantation SF affects outcome in patients undergoing allogeneic hematopoietic stem cell transplantation.


Choosing Fighting Competitors Among Men: Testosterone, Personality, and Motivations.
Higher testosterone levels have been positively related to a variety of social behaviors and personality traits associated with intrasexual competition. The aim of this study was to evaluate the role of testosterone levels and personality traits such as aggressiveness, competitiveness, and self-esteem on the task of choosing a fighting competitor (a rival) with or without a motivation to fight. In Study 1, a group of 119 men participated in a task for choosing a rival through pictures of men with high-dominant masculinity versus low-dominant masculinity. Participants completed three personality questionnaires and donated two saliva samples (pre-test and post-test sample) to quantify their testosterone levels. We found that the probability of choosing high-dominant masculine men as rivals increased with higher aggressiveness scores. In Study 2, the task of choosing rivals was accompanied by motivations to fight (pictures of women with high or low waist-to-hip ratio [WHR]). In this context, we observed that the probability of choosing dominant masculine men as rivals depended on the WHR of the women. Overall, average levels of post-test testosterone, aggressiveness, and high self-esteem increased the probability to fight for women with low WHR independently of the dominance masculinity of the rivals. Our results indicate that human decisions, in the context of intrasexual competition and mate choice, are regulated by physiological and psychological mechanisms allowing men to increase their biological fitness. We discuss our results in the light of the plasticity of human behavior according to biological and environmental forces.


Similarities and differences between pediatric and adult patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with highest prevalence among women of childbearing age. However, children younger than 16 years also can develop SLE (childhood-onset lupus/juvenile-type SLE). The aim of our study was to compare the clinical course of adult and pediatric-onset SLE. Data from 342 adult patients followed at the University of Debrecen, Hungary, and 79 children documented in the Hungarian National Pediatric SLE registry were analyzed using hospital medical records. Organ manifestations, laboratory parameters, and immunoserological characteristics were reviewed and the results were evaluated using SPSS for Windows software.Gender distribution was not significantly different between groups with disease starting in childhood vs adulthood. The prevalence of the following manifestations was significantly higher for pediatric than for adult-onset disease including: lupus nephritis (43% pediatric vs 26.4% for adult-onset), hematological disorders (57% vs 36.4%), photosensitivity (20% vs 9%), butterfly rash (61% vs 35.5%) and mucosal ulceration (11.4% vs 4%). For adult-onset SLE, neurological symptoms (30% vs 6%) and polyarthritis (86% vs 68%) occurred significantly more frequently than in children. Anti-SSA, anti-SSB and antiphospholipid antibodies were detected at significantly higher levels in adult-onset patients compared to those in pediatrics. Children were more commonly given high-dose intravenous immunoglobulin treatment (6.3% vs 0.6%) and mycophenolate mofetil (15.2% vs 5.3%) than adults.These results suggest that pediatric and adult-onset SLE differ in multiple aspects, and it is important to recognize these differences for optimal treatment and prognosis of these patients.


Weekend effects on binge drinking and homicide: the social connection between alcohol and violence in Russia.
This study employs unique newly available Russian mortality data to examine the social connection between binge drinking and homicide in the country. SETTING, PARTICIPANTS AND MEASUREMENTS: All death certificates of those aged 20-64 years in the Udmurt Republic, Russia, were analyzed according to day and cause of death for the years 1994-98. Deaths due to alcohol poisoning were used as a proxy for binge drinking. There was a high bivariate correlation (r = 0.75) between the daily distribution of deaths due to alcohol and homicide. The number of alcohol deaths was significantly higher on Saturdays and Sundays (presumably as a result of drinking on Friday and Saturday nights) and the number of homicide deaths was significantly higher on Fridays and Saturdays. The levels of alcohol consumption and homicide in Russia are among the highest in the world, and there is mounting evidence that the two are related. Binge drinking, preference for distilled spirits and a high social tolerance for heavy drinking may act as social and cultural contextual factors that might increase the risk of violent outcomes. The high correspondence between the daily distribution of alcohol and homicide deaths provides indirect evidence for the social connection between them. While these findings do not represent a causal connection, when placed in the context of the growing literature on this topic they provide further support of an association between alcohol consumption and homicide rates in Russia and preliminary evidence for the intermediate role in this relationship played by social context.


Self-selection of dietary protein and energy by broilers grown under a tropical climate: adaptation when exposed to choice feeding at different ages.
Three hundred broiler chicks (Hubbard) of both sexes were assigned to five feeding treatments: T0 received a complete diet (control), T1 was a choice feeding system with simultaneous access to an energy-rich feed (ground corn) and a protein concentrate (43.7% CP), and T2, T3, and T4 were introduced to choice feeding after 1, 3, and 5 wk, respectively, of consuming the complete diet. At 1-d-old, T1 chicks showed a marked preference for corn, with only 21.4% of their intake being the protein concentrate diet. Intake of the concentrate progressively increased to 40 to 45% after 3 d of adaptation, resulting in diets with 22.5 to 24.3% CP. When broilers fed the complete diet for 1 to 5 wk (T2, T3, T4) were changed to choice feeding, on the 1st d, their feed choice intake was similar to that of T1 chicks at the same age. Visual observation and tactile assessment of the feed particles during the initial period allowed the chicks to quickly evaluate the new feeds and to adapt their feeding behavior. Although total feed intake to 6 wk of age was not significantly affected by the feeding treatments, broilers on choice feeding selected diets with a lower percentage of CP and had lower live body weights at 6 wk than those fed the complete diet (T0).


Comparison of Expectant and Excisional/Ablative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in the Era of HPV Testing.
To investigate conservative and excisional/ablative treatment outcomes for cervical intraepithelial neoplasia grade 2 (CIN2) following introduction of virological test of cure. This was a retrospective study of prospectively collected data at a teaching hospital colposcopy unit. 331 sequential biopsy-proved CIN2 cases were involved. CIN2 cases diagnosed between 01/07/2014 and 31/12/2017 were either conservatively managed or treated with excision/ablation and then were followed up until discharge from colposcopy clinic and then using the national cervical cytology database. Outcomes were defined: cytological/histological regression was absence of high-grade CIN on biopsy and/or high-grade dysplasia; virological regression was cytological/histological regression and negative human papillomavirus testing; persistence was biopsy-proven CIN2 and/or moderate dyskaryosis; progression was biopsy-proven CIN3+ and/or severe dyskaryosis. Median follow-up was 22.6 months (range: 1.9-65.1 months). Among 175 (52.9%) patients initially managed conservatively, 77.3% (133/172) regressed, 13.4% (23/172) persisted, 9.3% (16/172) progressed to CIN3+, and 97 (56.4%) patients achieved virological regression. 156 (47.1%) patients underwent initial excision/ablation, with an 89.4% (110/123) virological cure rate. After discharge, 7 (4.0%) and 3 (1.9%) patients redeveloped CIN in the conservative and treatment groups, respectively, during a median period of 17.2 months. Conservative management is a reasonable and effective management strategy in appropriately selected women with CIN2. High rates of histological and virological regression should be expected. The previously mentioned data provide useful information for deciding management options.


Spatial accuracy of a rapid defense behavior in caterpillars.
Aimed movements require that an animal accurately locates the target and correctly reaches that location. One such behavior is the defensive strike seen in Manduca sexta larva. These caterpillars respond to noxious mechanical stimuli applied to their abdomen with a strike of the mandibles towards the location of the stimulus. The accuracy with which the first strike movement reaches the stimulus site depends on the location of the stimulus. Reponses to dorsal stimuli are less accurate than those to ventral stimuli and the mandibles generally land ventral to the stimulus site. Responses to stimuli applied to anterior abdominal segments are less accurate than responses to stimuli applied to more posterior segments and the mandibles generally land posterior to the stimulus site. A trade-off between duration of the strike and radial accuracy is only seen in the anterior stimulus location (body segment A4). The lower accuracy of the responses to anterior and dorsal stimuli can be explained by the morphology of the animal; to reach these areas the caterpillar needs to move its body into a tight curve. Nevertheless, the accuracy is not exact in locations that the animal has shown it can reach, which suggests that consistently aiming more ventral and posterior of the stimulation site might be a defense strategy.


Control of ColE1 plasmid replication. Intermediates in the binding of RNA I and RNA II.
Replication of plasmid ColE1 is regulated by a plasmid-specified small RNA (RNA I). RNA I binds to the precursor (RNA II) of the primer for DNA synthesis and inhibits primer formation. The process of binding of RNA I to RNA II that results in formation of a stably bound complex consists of a series of reactions forming complexes differing in the stability. Formation of a very unstable early intermediate that was previously inferred from the inhibition of stable binding caused by a second RNA I species was firmly established by more extensive studies. This complex is converted to a more stable yet reversible complex that was identified by its RNase sensitivity, which was altered from that of the earlier complex or from that of free RNA I or RNA II. In these complexes, most loops of RNA II interact with their complementary loops of RNA I. The kinetic and structural analyses of the binding process predict formation of a complex interacting at a single pair of complementary loops that precedes formation of these complexes. Thus the process of binding of RNA I to RNA II is seen to consist of a sequence of reactions producing a series of progressively more stable intermediates leading to the final product.